Expression of MiR-335 and its target metalloproteinase genes: clinical significance in breast cancer.

BACKGROUND: Early diagnosis of breast cancer decreases mortality rate; therefore, novel diagnostic methods are urgently required. In this study, authors aimed to investigate the role of serum-derived miR-335 in breast cancer, and the expression of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) and evaluating their feasibility and clinical utility as biomarkers for the early detection of breast cancer. MATERIALS AND METHODS: Blood samples were collected from a total of 210 individuals who were enrolled in this study. The participants were divided into newly diagnosed breast cancer patients (n = 115), patients with benign breast lesions (n =55) and healthy individuals as control group (n =40). The expression profile of miR-335, MMP2 and MMP9 were determined using quantitative polymerase chain reaction (qPCR). RESULTS: MiR 335 expression level was down-regulated in primary breast cancer group as compared to benign breast group and healthy individuals with 98% and 94.9% sensitivity and specificity, respectively. MMP2 and MMP9 showed significantly higher expression levels in breast cancer group as compared to both benign and healthy group and reporting 92.7% and 93% sensitivity, respectively. The relations between investigated markers and pathologic types, staging, grading, and lymph node involvement were significant with these factors. Expression level of miR-335 was decreased with increased MMP2 and MMP9 at significant level. CONCLUSION: MiR-335, MMP2, and MMP9 can be used as diagnostic markers in breast cancer.

Potential impact of stocking density on growth, carcass traits, indicators of biochemical and oxidative stress and meat quality of different broiler breeds.

The aim of the current study to investigate the potential impact of different stocking densities on growth performance, carcass traits, indicators of biochemical and oxidative stress and meat quality of Arbor Acres and Ross-308 broiler breeds to recommend the better stocking density with low production cost simultaneously with high quality. A total of 312 one-day old of each Arbor Acres broiler and Ross-308 were randomly classified into 3 experimental groups with different stocking density, each of 6 replicates. The first group (SD1) was 14 birds/m2 (28 kg/m2), while the second group (SD2) was 18 birds/m2 (36 kg/m2) and the third group (SD3) was 20 birds/m2 (40 kg/m2). The growth performance, carcass traits, meat quality hematological and biochemical parameters were measured. SD3 group possessed the lowest body weight. Alanine transaminase in Arbor Acres was 15 and 14% higher in SD3 when compared with SD1 and SD2, respectively. While, was 21 and 20% of Ross-308, respectively. SD3 revealed the highest values of cholesterol, TG, MDA, and LDL of both breeds when compared with SD1 and SD2, with the lowest levels of HDL, GPX, and IGG. Birds of SD3 was the nastiest carcass weight 873 (P = 0.000) and 1,411.60 g (P = 0.000); dressing percentage 63.07 (P = 0.000) and 75.83% (P = 0.000); breast weight 513.10 g (P = 0.000) and 885.50g (P = 0.000); thigh weight 359.90 g (P = 0.000) and 526.08 g (P = 0.000) when compared with SD1 and SD2 of Arbor Acres and Ross-308, respectively. The dressing % of SD1 and SD2 was approximately 19% better than that of SD3 of Arbor Acres, while it was 4% of Ross-308. The cooking loss and drip loss of breast and thigh muscles were higher in SD3 of both breeds. Moreover, SD3 possessed the highest bacterial count. In conclusion birds reared in medium stocking density revealed better performance and welfare than high density but similar to low density. Therefore, from the economic point, medium density was the best.

Intimate partner violence among Arab women before and during the COVID-19 lockdown.

INTRODUCTION: Intimate partner violence (IPV) remains a serious human rights violation and an important health concern during the ongoing COVID-19 pandemic. The study aims to estimate the proportion of IPV among adult Arab women before and during the COVID-19 lockdown and to identify its possible predictors during the lockdown. METHODS: A cross-sectional study was conducted between April and June 2020 using an online questionnaire. The sample included 490 adult Arab women aged 18 years and above, who live with their husbands. Data was collected using a Google forms designed questionnaire that included the socio-demographic characteristics, nature of lockdown, and exposure to different types of IPV before and during COVID-19 lockdown and the frequency of their occurrence. McNemar's test was used to determine differences in the exposure to IPV before and during the lockdown, while logistic regression analysis was performed to identify the predictors of exposure to IPV during the lockdown. RESULTS: Half of women reported that they were ever exposed to IPV with psychological violence ranking 1st. Exposure to any type of IPV and exposure to psychological, physical, and sexual violence have significantly increased during the lockdown compared to before the lockdown. The frequency of exposure to the different types of IPV ranged from 1-3 times per month to almost every day, but the most commonly reported was 1-3 times per month. Predictors of exposure to IPV during the COVID-19 lockdown included country of residence, family income, and whether the husband lost his job during lockdown. CONCLUSIONS: IPV has increased during the COVID-19 pandemic lockdown in the Arab countries, and it was associated with the socioeconomic consequences of the pandemic on families. Actions towards raising awareness about the problem among professionals and the community, early detection, and provision of appropriate services are mandatory.

Implications of targeted next-generation sequencing for bladder cancer: report of four cases.

BACKGROUND: Bladder cancer is considered heterogeneous diseases with two major subgroups: non-muscle- invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). It is a major healthcare problem, and it is one of the leading causes of mortality worldwide. Genetic mutations are not only a cause for carcinogenesis but are also a way for treatment strategy. The present study aimed to investigate breast cancer (BRCA genes) tumor suppressor gene mutations in bladder cancer tissue and combined blood samples for patients who developed secondary tumor after or during trimodal therapy. Fresh tissue samples and their matched blood samples were collected from four patients with bladder cancer. The objective regions for the examined genes (BRCA1 and BRCA2) were sequenced using next-generation sequencing (NGS); generated BAM files were uploaded to the cloud-based Ionreporter server, and the Oncomine BRCA-specific plugin was used to analyze the paired normal and tumor sample for each patient using the default plugin parameters. RESULTS: Intronic BRCA1 mutation c.5050-104 C >T was reported among the four investigated bladder cancer patients, and three somatic mutations were reported as follows: two of them were found to be benign rs1064793056 and rs28897679 on the Clinivar database and one nonsense pathogenic variant rs80357006. BRCA 2 gene mutation reported an exonic synonymous mutation rs397507876 in the tissue and germline DNA. Patients were treated with trimodal; however, three bladder cancer patients who reported BRCA mutations developed secondary tumors. CONCLUSION: Identification of mutational BRCA changes in bladder cancer is a promising marker for better treatment strategy. Further studies are encouraged on a large cohort of bladder cancer patients to confirm our findings.

Clinical impact of PTEN methylation status as a prognostic marker for breast cancer.

BACKGROUND: Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0-I, n = 48) and late stage (II-III, n = 64), and graded into low grade (I-II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. RESULTS: The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. CONCLUSIONS: PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.

Over-gene expression in the apoptotic, oxidative damage and liver injure in female rats exposed to butralin.

The present study is the first report for studying the toxic effects of butralin herbicide on COX2, BAX, and Bcl2 gene expression, oxidative stress, and liver damage in female rats. Female rats were received butralin in drinking water for 28 days at concentration 4.16, 312, and 3120 mg/L that corresponded to the acceptable daily intake (ADI), no observed adverse effect level (NOAEL), and 10 NOAEL, respectively. Butralin decreased body weights and increased relative liver weight of female rats exposed to high dose. It caused significant elevation in liver function enzymes, lipid peroxidation, and reactive oxygen species (ROS). Antioxidant enzymes were decreased in liver tissue by increasing the dose. Butralin induced over-expression in the apoptotic related genes including COX2, BAX, and Bcl2 and pathological alteration in the liver of female rats especially at a high dose. It can be concluded that butralin induced oxidative damage and liver injure. The mechanism of damage could be due to generate reactive oxygen species, and increase lipid peroxidation that causes over-expression in the apoptotic related genes including COX2, BAX, and Bcl2. From the Benchmark dose (BMD) approach, there is dose-dependent manner in body weight, AST, ALT, and ALP, and ALT is a very sensitive parameter.

Clinical significance of blood-based miRNAs as diagnostic and prognostic nucleic acid markers in breast cancer: Comparative to conventional tumor markers.

microRNAs (miRNAs) are implicated in carcinogenesis and their expression in biological fluids offer great potential as nucleic acid markers for cancer detection and progression. Authors investigated the expression level of miRNAs (miRNA-21, miRNA-126, and miRNA-155) to evaluate their role as diagnostic and prognostic markers for breast cancer compared with other commonly used protein-based markers (CEA and CA15-3). Serum samples from patients with breast cancer (n = 96), patients with benign breast lesion (n = 47), and healthy individuals (n = 39) were enrolled for detection of miRNA expression levels and protein-based tumor markers using fluorescent real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Correlation among investigated markers with clinicopathological factors and clinical outcomes were determined. Expression of miRNA-21 and miRNA-155 revealed significant increases in patients with breast cancer compared with both benign and control groups, the same result was reported for tumor markers; on the other hand, miRNA-126 was significantly decreased in breast cancer group as compared with the other two groups. miRNA frequencies were significantly related to clinical staging and histological grading as compared with tumor markers. Patients with breast cancer with increased miRNA-21 and miRNA-155 and decreased miRNA-126 expressions had significantly worse disease-free survival, while only miRNA-21 and miRNA-126 showed poor OS (P< 0.005). In conclusion, investigated miRNAs were superior over tumor markers for the early stage of breast cancer especially those with high-risk factor and their assessment in blood facilitates their role as a potential prognostic molecular marker.

Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer commonly affecting children due to dysregulation of miRNA expression. In the current study, authors investigated the expression profile for miRNA-125b-1 and miRNA-203 among childhood ALL. Blood samples were collected from newly diagnosed childhood ALL and healthy control children. The expression profile for candidate miRNAs was detected using quantitative RT-PCR analysis. Statistical analysis were performed using receiver operating characteristic curve (ROC) to examine the diagnostic efficacy of the two miRNA and their levels among ALL clinicopathological factors and phenotypes. The median expression level for miRNA-125b-1 was significantly high in childhood ALL; while miRNA-203 level was significantly low in childhood ALL as compared to control ones. MiRNA-125-1 reported significant increase in T-ALL as compared to other ALL phenotypes. Median miRNA-203 level was high in T-ALL followed by pre-B-ALL although no significant difference was reported. Clinicopathological factors did not emphasize significance with either detected miRNAs. Using ROC curve the diagnostic efficacy was significant with an area under the curve 0.858 for miRNA-125b-1 (83.72, 100%) and 0.878 for miRNA-203 (97.67, 86.96%). The combination of the two key miRNAs revealed absolute sensitivity (100%). MiRNA-125b-1 and miRNA-203 can be useful molecular markers for diagnosis of ALL. Further studies with large cohort are warranted to validate these results.

Aberrant methylation of APC and RARß2 genes in breast cancer patients.

Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. We aimed to identify epigenetic molecular markers in serum for early detection of breast cancer. Authors analyzed retrospectively the methylation status of RARß2 and APC genes in serum samples from 121 breast cancer patients, 79 patients with benign breast diseases, and 66 healthy volunteers using methylation-specific PCR. The methylated APC and RARß2 were significantly higher in breast cancer patients (93.4%, 95.6%) than benign (7.8%, 14.5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathological factors apart from triple negative breast cancer patients as all of them (χ(2) = 7.4, P = 0.007) reported to be methylated RARß2 genes. Both methylated genes were detected in all grades and stages. Both sensitivities and specificities of the methylated genes for breast cancer detection were superior to traditional tumor markers in detection of breast cancer, early stage, low grade tumors, and triple negative breast cancer patients. Thus methylated APC and RARß2 genes might be valuable serum-based molecular markers for early detection of breast cancer.

Oxidative damage and nephrotoxicity induced by prallethrin in rat and the protective effect of Origanum majorana essential oil.

OBJECTIVE: To investigate the effects of prallethrin on renal dysfunction biomarkers, antioxidant enzyme activities and lipid peroxidation (LPO) in rats and the protective effect of Origanum majorana essential oil. METHODS: Rats were divided into four groups of seven rats in each group: (I) received only olive oil, (II) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) in olive oil via oral route daily for 28 d, (III) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) and essential oil (160 µL/kg body weight) in olive oil and (IV) received essential oil (160 µL/kg body weight) in olive oil via oral route twice daily for 28 d. RESULTS: Prallethrin caused significant increase in LPO and decrease in superoxide dismutase, glutathione peroxidase and glutathione reduced. Consistent histological changes were found in the kidney of prallethrin treatment. Co-administration of essential oil attenuated the prallethrin induced renal toxicity and oxidative stress by decreasing LPO in kidney, creatinine, urea and uric acid levels in serum. In addition, superoxide dismutase, glutathione peroxidase activity and glutathione reduced level were increased in kidney in prallethrin-essential oil groups. CONCLUSIONS: We can conclude that prallethrin induced oxidative damage and renal toxicity in male rat. The administration of essential oil provided significant protection against prallethrin-induced oxidative stress, biochemical changes and histopathological damage.

Antimutagenic effect of Origanum majorana L. essential oil against prallethrin-induced genotoxic damage in rat bone marrow cells.

This study aimed to investigate the genotoxic and cytotoxic potential of prallethrin in rat bone marrow cells and the protective effect of Origanum majorana L. essential oil (EO). Our results demonstrated that prallethrin at dose 64.0 mg/kg body weight (b.wt.) (1/10 LD50), has a clastogenic/genotoxic potential as shown by the high percentage of chromosomal aberration (CA) and micronucleus (MN) in the bone marrow cells of male rats, whereas the combined treatment of prallethrin and O. majorana EO resulted in the reduction of the CA (54.54%). The combined treatment also reduced the micronuclei formation significantly. In conclusion, prallethrin can be considered clastogenic/genotoxic and may carry a risk to human health. The study revealed the antigenotoxic and anticytotoxic potential of O. majorana EO against prallethrin-induced genotoxic and cytotoxic effects in rat bone marrow cells.

Serum adiponectin and resistin levels in de novo and relapsed acute lymphoblastic leukemia children patients.

BACKGROUND: Adipose tissue secretes a large number of adipocytokines such as leptin, resistin, and adiponectin. Many of these hormones and cytokines are altered in obese individuals and may lead to disruption of the normal balance between cell proliferation, differentiation, and apoptosis. The aim of our work was to investigate the disturbance of secretion of adiponectin and resistin in de novo and relapsed acute lymphoblastic leukemia (ALL) in Egyptian children and determine whether adiponectin and resistin are implicated in increased risk relapse compared to healthy individuals. METHODS: Measurements of adiponectin and resistin were performed at diagnosis, in 32 patients with de novo ALL aged 3 to 18 years (mean 9.8 y) and 19 children with relapsed ALL aged 5 to 17 (mean 9.9 yr). 10 apparently healthy children with matched age and sex were used as controls. RESULTS: Mean adiponectin levels were low (P < 0.05), whereas mean resistin levels were high (P<0.05) at diagnosis and relapsed ALL (compared to healthy controls). A significant decrease of adiponectin levels was observed in relapsed ALL compared to de novo ALL. In contrast resistin was significantly increased in relapsed ALL compared to de novo patients. Adiponectin in ALL subjects inversely correlated with resistin level (r = -0.51, P < 0.001). CONCLUSION: Low adiponectin and high resistin level at diagnosis suggest their implication in ALL pathogenesis and may serve as potential clinically significant diagnostic markers to detect leukemic relapse.

Amelioration of prallethrin-induced oxidative stress and hepatotoxicity in rat by the administration of Origanum majorana essential oil.

This study was carried out to evaluate the adverse effects of exposure to prallethrin on oxidant/antioxidant status and liver dysfunction biomarkers and the protective role of Origanum majorana essential oil (EO) in rat. Male rats were divided into 4 groups: (i) received only olive oil (ii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) in olive oil via oral route daily for 28 days, (iii) treated with 64.0 mg/kg body weight prallethrin (1/10 LD50) and EO (160 µL/kg b.wt.) in olive oil and (iv) received EO (160 µL/kg b.wt.) in olive oil via oral route twice daily for 28 days. Prallethrin treatment caused decrease in body weight gain and increase in relative liver weight. There was a significant increase in the activity of serum marker enzymes, aspartate transaminase, alanine transaminase, and alkaline phosphatase. It caused increase in thiobarbituric acid reactive substances and reduction in the activities of superoxide dismutase, catalase, and glutathione-S-transferase in liver. Consistent histological changes were found in the liver of prallethrin treatment. EO showed significant protection with the depletion of serum marker enzymes and replenishment of antioxidant status and brought all the values to near normal, indicating the protective effect of EO. We can conclude that prallethrin caused oxidative damage and liver injury in male rat and co-administration of EO attenuated the toxic effect of prallethrin. These results demonstrate that administration of EO may be useful, easy, and economical to protect human against pyrethroids toxic effects.

Common forms of atresia in the ovary of some Red Sea fishes during reproductive cycle.

Four economic fish species were collected monthly from commercial catch land at El-Attaka fish landing (Saurida undosquamis, Rhabdosargus haffara, Nemipterusjaponicus and Liza carinata). Histoligical examination of ovaries of these species indicated the presence of atretic oocytes (oocyte retention) as a natural phenomenon in fishes. Depending on the histological descriptions atretic oocytes may be classified into two main types: a, bursting b, non bursting. In the present study, frequency of degenerating oocytes were affected by the gonad maturation. In the early stages, the frequency is very low. It increased gradually reaching its maximum in spent stage about 50%. There is a significant difference between the atretic oocytes and gonad maturation (p < 0.05). Atresia is also affected by the length of the spawning season (Long or short). All examined ovaries of multiple spawners (S. undosquamis) should atretic oocytes. But in (N. japonicus, R. haffara and L. carinata) about 30 to 35% of the ova show atresia. These species have limited spawning season.