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The data-driven Artificial Intelligence (AI) techniques revealed specific relevance for the treatment of nonlinear relations and predicting the behaviour of complex systems, as a promising application in hydrology and water quality problems. The goal of this study is to build a developed model to forecast the quality of irrigation water by estimating its Water Quality Index using Artificial Neural Network (ANN). The developed model is applied to predict a data-based Irrigation Water Quality Index (IWQI) for groundwater usability in a desert reach pilot area in Egypt. The raw data for the model were the results of the main ion-causing irrigation hazards: (Salinity & Infiltration rate& Specific Toxics and Miscellaneous effects) for seventy-seven groundwater samples. The effectiveness of the model was achieved through the standardized coefficient of input variables. Revealing that the developed ANN model has a high agreement between measured and calculated IWQI (R2= 0.963, RMSE=0.0693) and becomes satisfactory verified for predicting the overall quality of groundwater in the research region, which is based on individual measurements rated according to their sensitivity. Moreover, the newly developed model can overcome the problem of missing some sample index parameters when one or more of the parameters are missing.

This study aimed to evaluate the presence of coliforms in 50 samples (25 ready-to-eat vegetable salads and 25 handlers’ hands) collected randomly from restaurants in Baghdad. The total coliform count in the samples of vegetable salads from Al-Sadria and Hay al-Amel reached 4.78 and 4.32 log cfu/g, respectively, whereas those in the swab samples of handlers’ hands from the same areas reached 3.70 and 3.90 log cfu/g, respectively. The percentages of fecal coliform bacteria in the salad samples from Al-Sadria and Hay al-Amel were 35% and 32%, respectively, whereas those in the hand swabs from the same areas were 41% and 36%, respectively. Two isolates of the serotype Escherichia coli O157:H7 were detected in the study samples from the same areas, where the rates of E. coli and fecal coliform bacteria increased. Considering the virulence of this bacterial serotype and its direct impact on consumer safety, we highly recommend implementing quality programs in ready-to-eat vegetable salad production chains, raising the cultural level and health awareness of restaurant owners and workers preparing these salads, and raising public awareness of the potential health risks of consuming contaminated food products.

The efficiency of partial body weight-supported treadmill training (PBWSTT) for treating various conditions in children and adolescents with cerebral palsy (CP) in diverse contexts of rehabilitation, households, or schools is unknown. The major objective of this systematic review and meta-analysis was to analyze the effectiveness of PBWSTT on various outcomes in different contexts among children and adolescents with CP. We incorporated full-text, randomized controlled trial studies that specifically assessed the effects of PBWSTT walking, motor function, stride, balance, and endurance in children and adolescents aged 3 to 18 years with CP. The literature search was carried out using Google Scholar, PubMed, Web of Science, CINAHL Plus, Scopus, PEDro, and ResearchGate databases. The methodological quality was evaluated using a Cochrane risk of bias instrument. A meta-analysis of pooled data from 10 studies with 255 participants demonstrated that PBWSTT for 4–12 weeks in rehabilitation (mean difference [MD] = 1.94, 95% confidence interval [CI] = 1.40—2.48, p < 0.0001), at home or in a school context (MD = 13.5, 95% CI = 13.9—16.0, p < 0.0001), was significantly effective for treating various conditions in children and adolescents suffering with CP. The period of 4–12 weeks of PBWSTT in rehabilitation and at-home/school settings is effective on various outcomes in children or adolescents with CP.

Background. The Functional Rating Index (FRI) is a self-report scale widely used to determine the level of disability in low back pain (LBP) populations. Objectives. This study was aimed at conducting the cross-cultural adaptation of the FRI-Arabic version (FRI-Ar) and testing the clinometric properties of FRI-Ar. Methods. The cross-cultural adaptation process was used to develop the FRI-Ar. This study included acute and subacute LBP patients. Each patient was asked to complete the questionnaires at three time points: baseline, 24-hour follow-up, and two-week follow-up. The questionnaires used were FRI-Ar, Roland-Morris Disability Questionnaire (RMDQ), Oswestry Disability Index (ODI), Numerical Pain Rating Scale (NPRS), Global Perceived Effect Scale (GPE), and Patient-Specific Functional Scale (PSFS). Statistical analysis was carried out to measure the instrument’s reliability, validity, and responsiveness. Results. The FRI was cross-culturally adapted to the Arabic language, and the adapted version was validated. Two hundred patients completed the questionnaires at the baseline; however, 120 patients completed the questionnaires at 24-hour and two-week follow-up. Cronbach’s alpha, interclass correlation coefficient (ICC2,1), standard error of measurement (SEM), and minimal detectable change (MDC95%) for the FRI-Ar were observed as 0.85, 0.85, 1.17 (2.9%), and 3.24, respectively. The FRI-Ar showed a moderate positive correlation only with the RMDQ, ODI, and NPRS (p

An L-shaped structure, intended for piezoelectric energy harvesting, is being characterized numerically to obtain extended insight into the effect of various parameters and metrics that are hard to track from experimental setups and simplified analytical models and to show the underlying mechanism of efficient piezoelectric harvesting. A numerical model was developed to analyze the structure under harmonic base excitation to obtain voltage frequency response and strain distribution data. The model takes into effect the load resistance applied between the piezoelectric patch electrodes and the damping ratio of each mode for accurate resonance amplitude evaluation. The validity of the model was confirmed by comparisons with previous experiments and showed strong agreement. The approach demonstrated that piezoelectric energy harvesting modeling, in general, is sensitive to inaccurate estimations, especially in the damping parameters, which emphasizes that rough assumptions made in analytical models will not yield results that can be discussed in correlation with experimental outcomes. This work states the guidelines for accurate piezoelectric modeling using numerical software, with the aim of enabling the investigation of complex harvesters, providing more insights to direct researchers to more proof and optimized designs that tackle broadband and energy density problems found in simple harvesters. [ABSTRACT FROM AUTHOR]

Food contamination has significant effects on consumers' health. The present study aimed to estimate some heavy elements (copper, manganese, nickel, lead, cadmium, chromium, zinc, and iron) and quantify the residuals of pyrethroid pesticides such as cypermethrin, deltamethrin, permethrin, and bifenthrin in coffee products in the markets of Baghdad city. Coffee available in the market was from Brazil, Ethiopia, India, Kenya, Uganda, Indonesia, Guatemala, and Colombia, and 24 different samples were used for the study. The concentrations of heavy metals were estimated using the atomic absorption technique, while the pesticide residues were calculated using the LC-MS technique. The results showed that the copper, manganese, nickel, and zinc concentrations for all coffee samples were within acceptable limits. As for the concentrations of chromium and iron, some samples exceeded the permissible limits, such as the highest concentration of chromium was 1.137 mg/kg, and that iron was 57.089 mg/kg. The pyrethroid residues were high, and cypermethrin, deltamethrin, permethrin, and bifenthrin were on the higher side than the permissible levels and were recorded as 0.437, 0.833, 1.063, and 0.753 mg/kg, respectively, exceeding the maximum limits set by international standards. [ABSTRACT FROM AUTHOR]

Copyright of Iraq Journal of Market Research & Consumer Protection / Al-Mağallaẗ al-ʿIrāqiyyaẗ li-Buḥūṯ al-Sūq wa-Ḥimāyaẗ al-Mustahlik is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction/Objective: Breast cancer (BC) is the first leading cause of cancer-related mortality in females worldwide. We have investigated the correlation between circ-ITCH gene polymorphisms, circ-ITCH expression, and their effect on β-catenin levels and BC development. Methods: Participants included 62 BC and 62 controls matched in terms of age. The circ-ITCH polymorphisms rs10485505 and rs4911154 were genotyped using whole blood samples. In addition, mRNA expression analysis of circ-ITCH was performed on BC tissues. The β-catenin levels in serum samples were measured using ELISA. Results: The qRT-PCR results demonstrated that circ-ITCH was significantly downregulated in BC compared to normal healthy tissues. The genotype distribution of rs10485505 and rs4911154 were significantly associated with BC risk. For rs10485505, genotype CT and TT were significantly associated with an increased BC risk. In contrast, there was a significant association between rs4911154, genotypes GA and AA, and an increased BC risk. Regarding the rs10485505 genotype, carriers of the T allele frequently have a poor prognosis compared to carriers of the CC genotype. Serum β-catenin in the BC patients' group was significantly higher than in the control group. The relative expression levels of circ-ITCH were remarkably decreased in the BC samples of patients carrying the A allele at rs4911154 compared to patients with a GG genotype. Conversely, β-catenin protein levels were increased in patients carrying the A allele, while rs10485505 genotype carriers of the CT and TT genotypes showed downregulation of circ-ITCH expression fold compared to the CC genotype. Contrarily, β-catenin levels markedly increased in TT and CT genotypes compared with the CC genotype. Conclusions: Our research showed that the rs10485505 polymorphism (T allele) and the rs4911154 polymorphism (A allele) are associated with the risk and prognosis of BC. This finding may be due to the effect on the level of circ-ITCH mRNA expression in BC tissues as well as the level of β-catenin in BC patients. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the presence of coliforms in 50 samples (25 ready-to-eat vegetable salads and 25 handlers' hands) collected randomly from restaurants in Baghdad. The total coliform count in the samples of vegetable salads from Al-Sadria and Hay al-Amel reached 4.78 and 4.32 log cfu/g, respectively, whereas those in the swab samples of handlers’ hands from the same areas reached 3.70 and 3.90 log cfu/g, respectively. The percentages of fecal coliform bacteria in the salad samples from Al-Sadria and Hay al-Amel were 35% and 32%, respectively, whereas those in the hand swabs from the same areas were 41% and 36%, respectively. Two isolates of the serotype Escherichia coli O157:H7 were detected in the study samples from the same areas, where the rates of E. coli and fecal coliform bacteria increased. Considering the virulence of this bacterial serotype and its direct impact on consumer safety, we highly recommend implementing quality programs in ready-to-eat vegetable salad production chains, raising the cultural level and health awareness of restaurant owners and workers preparing these salads, and raising public awareness of the potential health risks of consuming contaminated food products. [ABSTRACT FROM AUTHOR]

Seawater desalination is considered a non-conventional source for suitable drinking water supply; still considerations about negatively environmental adverse effects are raised. Disposal of rejected brine represents major environmental challenges for most desalination plants. The aim of this paper is to explore the adverse environmental impacts of entailing huge amounts of brine into the local coastal aquifer along the Red Sea coast of Sharm El-Sheikh area, South Sinai. Brine water and ten production wells of the largest water desalination plant; El-Montazah, were sampled for all available chemical and trace elements analysis. The speciation and saturation with respect to minerals have been done using geochemical modeling indicating super-saturation of dolomite in feed water, while; calcite and dolomite were supersaturated minerals in brine water. Mathematical modeling of groundwater flow using MODFLOW-2000 was applied with variably-density miscible salt transport using SEAWAT code governing equations applying three different scenarios up to 50 y was used to investigate and predict the impact of brine disposal on the coastal aquifer. Simulation results indicate that; Miocene aquifer was affected by both sea water intrusions (laterally) and the effluent of brine water through the injection well (vertically). Some Mitigation actions were recommended to lessen the harmful and destructive environmental impacts of brine water disposal. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is one of the leading causes of cancer mortality in women. Glutathione S‐transferase (GSTT1) is involved in activation of detoxification reactions and catalysis of chemicals conjugation with glutathione. GSTT1 genotype is a limiting factor for some environmental diseases. Epigenetic changes have an essential role in BC through inappropriate interaction between genomic and environmental risk factors. Aim: This study was directed to explore the association of BC risk with GSTT1 genetic variations and its methylation status in Egyptian women. Design and Methods: This study included 100 healthy women as the control group and 100 patients were clinically and histologically diagnosed with breast cancer. All blood samples were used for genomic DNA extraction. GSTT1 genotyping was accomplished by multiplex PCR and methylation‐specific PCR was used to analyze the GSTT1 promoter methylation status. Results: Breast cancer patients showed significant incidence of null GSTT1 in relation to controls (p = 0.004). GSTT1 gene promoter methylation status showed significant difference between hypermethylated and unmethylated patients when compared with healthy subjects (p = 0.005). GSTT1 promoter methylation status was not significantly associated with null genotype. There was no significant association between GSTT1‐null genotypes and BC stage in cases with or without family history, but for promotor methylation, there was significant association with stage III and IV breast cancer disease. Conclusion: GSTT1 null genetic variant and promoter hypermethylation in the GSTT region of the gene may be considered as critical risk factors for BC in Egyptian women. [ABSTRACT FROM AUTHOR]

There is growing evidence in support of ischemic stroke as a manifestation of COVID-19 infection. However, hemorrhagic transformation of ischemic stroke is rare. We present two cases of hemorrhagic infarction as presenting features in COVID-19 patients who did not have traditional cardiovascular risk factors for ischemic or hemorrhagic stroke. While the hemorrhagic infarct was from a large artery in one of the patients, the other patient had a small artery related hemorrhagic infarct. We highlighted the possible underlining mechanisms from the literature and the implication of hemorrhagic infarct for routine anticoagulant therapy in patients with COVID −19 related ischemic stroke. [ABSTRACT FROM AUTHOR]

Punching shear is one of the critical concerns in the design of flat slab systems. This research is conducted to investigate the effect of different parameters regarding shear reinforcement on the punching strength of flat slabs. These parameters include yield stress of stirrups, extension of stirrups from column face along slab span, slab thickness, and the shape of stirrups whether multiple leg stirrups or closed stirrups. The experimental program in this research included testing eight slab specimens with dimensions of 1200 × 1200 mm and a thickness of 160 mm and 200 mm. The results of the experimental work were compared to those estimated according to local and international building codes. The results showed that using closed stirrups greatly increased the punching capacity of flat slabs even for a thickness of 160 mm. [ABSTRACT FROM AUTHOR]

In this paper, we consider the downlink of a multi-user multiple-input-multiple-output system operating at the millimeter wave band in an outdoor environment. In this band, receive spatial modulation (RSM) schemes have been shown to achieve good spectral efficiency-energy consumption trade-off for the single-user case by exploiting new transceiver architectures that use a single radio-frequency (RF) chain at the user terminal (UT). In this work, we propose a novel RSM scheme for multiple RF chains at the UT. With the goal of maximizing the spectral efficiency (SE), we consider analog switches at the UT that select which antennas are active. To minimize the power consumption at the BS, we include analog switches that control the ON/OFF status of RF chains such that the SE is higher than a given threshold. Moreover, we extend the RSM concept to multiple users transmission. Specifically, we propose an algorithm that jointly optimizes the number of users, set of antennas and transmit power allocated to each user to maximize the sum SE. Simulation results show that RSM outperforms conventional modulation (no spatial symbols are transmitted) in terms of spectral and energy efficiency. Moreover, the proposed algorithms tightly approach the exhaustive search and outperform the prior art in terms of performance and convergence. [ABSTRACT FROM AUTHOR]

We consider a point to point large-scale multiple-input multiple-output (MIMO) system operating in the millimeter wave (mmWave) band and an outdoor scenario. Novel transmit and receive spatial modulation (SM) schemes are proposed for uplink (UL) and downlink (DL) data transmission phases based on a novel energy efficient hybrid user terminal architecture. The analog circuitry of the proposed hybrid architecture is divided into two stages: phase shifters and analog switches. The phase shifting stage assures high gain and overcomes the severe path-loss caused by outdoor mmWave propagation. The analog switching stage smartly allocates the antennas to be used at the phase shifting stage and combats the spatial correlation. We provide the analysis of the spectral efficiency $({{SE}})$ of the UL and DL systems. Next, we propose a reduced complexity algorithm that jointly optimizes the analog beamformer and combiner design of the UL and DL circuitry to maximize the energy efficiency $({{EE}})$. Finally, we compare and evaluate the performance of the proposed algorithm in terms of the ${{SE}}$ and ${{EE}}$ assuming both stochastic and realistic channel models. [ABSTRACT FROM AUTHOR]

Background and aim. DNA methylation plays a critical role in the control of important cellular processes. The present study assessed the impact of promoter methylation (PM) of some genes on the antiviral response to antiviral therapy and it's relation to the presence of fibrosis in HCV-4 infected patients from Egypt. Material and methods. Clinical, laboratory and histopathological data of 53 HCV-4 infected patients who were subjected to combined antiviral therapy were collected; patients were classified according to their response to treatment and the fibrosis status. The methylation profiles of the studied groups were determined using the following genes: APC, P14ARF, P73, DAPK, RASSF1A, and O6MGMT in patients' plasma. Results. O6MGMT and P73 showed the highest methylation frequencies (64.2 and 50.9%) while P14 showed the lowest frequency (34%). Sustained virological response (SVR) was 54.7%with no significant difference in clinico-pathological or laboratory features between the studied groups. PM of O6MGM was significantly higher in non-responders (p value 0.045) while DAPK showed high methylation levels in responders with no significance (p value: 0.09) and PM of RASSF1A was significantly related to mild fibrosis (p value: 0.019). No significant relations were reported between PM of any of the studied genes and patients' features. Conclusion. PM of some Tumor Suppressor genes increases in chronic active HCV-4. However, only 06MGMT can be used as a predictor of antiviral response and RASSF1A as a marker of marked fibrosis in this small set of patients. An extended study, including more patients is required to validate the results of this preliminary study. [ABSTRACT FROM AUTHOR]

The FVB/N mouse strain is extensively used in the development of animal models for breast cancer research. Recently it has been reported that the aging FVB/N mice develop spontaneous mammary lesions and tumors accompanied with abnormalities in the pituitary glands. These observations have a great impact on the mouse models of human breast cancer. We have developed a population of inbred FVB/N mice (designated FVB/N-RC) that have been genetically isolated for 20 years. To study the effects of age and parity on abnormalities of the mammary glands of FVB/N-RC mice, twenty-five nulliparous and multiparous (3-4 pregnancies) females were euthanized at 16-22 months of age. Examination of the mammary glands did not reveal macroscopic evidence of mammary gland tumors in either aged-nulliparous or multiparous FVB/N-RC mice (0/25). However, histological analysis of the mammary glands showed rare focal nodules of squamous changes in 2 of the aged multiparous mice. Mammary gland hyperplasia was detected in 8% and 71% of the agednulliparous and aged-multiparous mice, respectively. Epithelial contents and serum levels of triiodothyronine were significantly higher in the experimental groups than the 14-wk-old control mice. Immuno-histochemical staining of the pituitary gland pars distalis showed no difference in prolactin staining between the control and the aged mice. Tissue transplant and dilution studies showed no effect of age and/or parity on the ability of putative progenitor cells present among the injected mammary cells to repopulate a cleared fat pad and develop a full mammary gland outgrowth. This FVB/ N-RC mouse substrain is suitable to develop mouse models for breast cancer. [ABSTRACT FROM AUTHOR]

Rspo2 was identified as a novel common integration site (CIS) for the mouse mammary tumor virus (MMTV) in viral induced mouse mammary tumors. Here we show that Rspo2 modulates Wnt signaling in mouse mammary epithelial cells. Co-expression of both genes resulted in an intermediate growth phenotype on plastic and had minor effects on the growth-promoting properties of Wnt1 in soft agar. However, individual Rspo2 and Wnt1 HC11 transfectants as well as the double transfectant were tumorigenic in athymic nude mice, with tumors from each line having distinctive histological characteristics. Rspo2 and Rspo2/Wnt1 tumors contained many spindle cells, consistent with an epithelial-mesenchymal transformation (EMT) phenotype. When Rspo2 and Rspo2/Wnt1 tumor cells were transferred into naïve mice, they exhibited greater metastatic activity than cells derived from Wnt1 tumors. For comparison, C57MG/Wnt1/Rspo2 co-transfectants exhibited invasive properties in three-dimensional (3D) Matrigel cultures that were not seen with cells transfected only with Wnt1 or Rspo2. Use of Dickkopf-1, a specific antagonist of the Wnt/β-catenin pathway, or short hairpin RNA targeting β-catenin expression demonstrated that the invasive activity was not mediated by β-catenin. Our results indicate that Rspo2 and Wnt1 have mutually distinct effects on mammary epithelial cell growth and these effects are context-dependent. While Rspo2 and Wnt1 act synergistically in the β-catenin pathway, other mechanisms are responsible for the invasive properties of stable double transfectants observed in 3D Matrigel cultures. J. Cell. Physiol. 227: 1960-1971, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Notch genes play a critical role in mammary gland growth, development and tumorigenesis. In the present study, we have quantitatively determined the levels and mRNA expression patterns of the Notch receptor genes, their ligands and target genes in the postnatal mouse mammary gland. The steady state levels of Notch3 mRNA are the highest among receptor genes, Jagged1 and Dll3 mRNA levels are the highest among ligand genes and Hey2 mRNA levels are highest among expressed Hes/Hey target genes analyzed during different stages of postnatal mammary gland development. Using an immunohistochemical approach with antibodies specific for each Notch receptor, we show that Notch proteins are temporally regulated in mammary epithelial cells during normal mammary gland development in the FVB/N mouse. The loss of ovarian hormones is associated with changes in the levels of Notch receptor mRNAs ( Notch2 higher and Notch3 lower) and ligand mRNAs ( Dll1 and Dll4 are higher, whereas Dll3 and Jagged1 are lower) in the mammary gland of ovariectomized mice compared to intact mice. These data define expression of the Notch ligand/receptor system throughout development of the mouse mammary gland and help set the stage for genetic analysis of Notch in this context. J. Cell. Physiol. 226: ??-??, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostaining and Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland. J. Cell. Physiol. 216: 824–834, 2008, © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Discusses research being done on the role of netrin-1 in the invasion and migration of mouse mammary epithelial cells. Reference to a study by Luigi Strizzi and colleagues, published in a 2005 issue of the "Journal of Cell Science"; Association of the overexpression of Cripto-1 in the epithelial cells with netrin-1; Alteration of the ductal growth of mammary glands overexpressing Cripto-1.

Background: Vitiligo is acquired depigmentary disorder characterized by destruction of the epidermal melanocytes leading to the loss of the skin color. Oxidative stress has a major role in the aetiopathogenesis and in melanocytic destruction due to its accumulation in the melanocytes and the hazardous effects to all compartments of the cell. Objective: The aim of the work was to evaluate the level of Ecadherin and H2O2 level in vitiligo versus controls. Subjects: This is a case control study which was carried out at Department of Dermatology, Venereology and Andrology, New Cairo Police Academy Hospital on 20 Subjects were divided into two groups, Group I included 10 patients having non segemental vitiligo. Group II included 10 non vitilignous controls were included in the study. Results: We found that H2O2 level is increased in NSV patients when compared with healthy individuals. While E-cadherin level is significantly decreased in vitiligo skin compared to normal skin. Conclusion: As compared to controls, increased H2O2 levels levels were suggestive of oxidative stress in patients of vitiligo in our study. From our results we can conclude that vitiligo is not a disease confined to melanocytes only, keratinocytes also showed certain pathological changes in vitiliginous lesions. As functional and structural units with melanocytes, keratinocytes in depigmented epidermis may constitute a different microenvironment compared to those in normally pigmented epidermis. These differences include obvious loss of cell to cell adhesion between keratinocytes and melanocytes and between keratinocytes and each other, which in turn may affect the pigmentary system of the skin. [ABSTRACT FROM AUTHOR]

Notch receptors and their ligands have crucial roles in development and tumorigenesis. We present evidence demonstrating the existence of an antagonistic relationship between Notch 4 and Trp53, which is controlled by the Mdm2-dependent ubiquitylation and degradation of the Notch receptor. We show that this signal-controlling mechanism is mediated by physical interactions between Mdm2 and Notch 4 and suggest the existence of a trimeric complex between Trp53, Notch 4 and Mdm2, which ultimately regulates Notch activity. Functional studies indicate that Trp53 can suppress NICD4-induced anchorage-independent growth in mammary epithelial cells and present evidence showing that Trp53 has a pivotal role in the suppression of Notch-associated tumorigenesis in the mammary gland. [ABSTRACT FROM AUTHOR]

Background: Hepatobiliary manifestations occur in ulcerative colitis (UC) patients. The effect of laparoscopic restorative proctocolectomy (LRP) with ileal pouch anal anastomosis (IPAA) on hepatobiliary manifestations is debated., Aim: To evaluate hepatobiliary changes after two-stages elective laparoscopic restorative proctocolectomy for patients with UC., Methods: Between June 2013 and June 2018, 167 patients with hepatobiliary symptoms underwent two-stage elective LRP for UC in a prospective observational study. Patients with UC and having at least one hepatobiliary manifestation who underwent LRP with IPAA were included in the study. The patients were followed up for four years to assess the outcomes of hepatobiliary manifestations., Results: The patients' mean age was 36 ± 8 years, and males predominated (67.1%). The most common hepatobiliary diagnostic method was liver biopsy (85.6%), followed by Magnetic resonance cholangiopancreatography (63.5%), Antineutrophil cytoplasmic antibodies (62.5%), abdominal ultrasonography (35.9%), and Endoscopic retrograde cholangiopancreatography (6%). The most common hepatobiliary symptom was Primary sclerosing cholangitis (PSC) (62.3%), followed by fatty liver (16.8%) and gallbladder stone (10.2%). 66.4% of patients showed a stable course after surgery. Progressive or regressive courses occurred in 16.8% of each. Mortality was 6%, and recurrence or progression of symptoms required surgery for 15%. Most PSC patients (87.5%) had a stable course, and only 12.5% became worse. Two-thirds (64.3%) of fatty liver patients showed a regressive course, while one-third (35.7%) showed a stable course. Survival rates were 98.8%, 97%, 95.8%, and 94% at 12 mo, 24 mo, 36 mo, and at the end of the follow-up., Conclusion: In patients with UC who had LRP, there is a positive impact on hepatobiliary disease. It caused an improvement in PSC and fatty liver disease. The most prevalent unchanged course was PSC, while the most common improvement was fatty liver disease., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal mammary gland development but still developed mammary tumors with a slightly longer latency than the WAP-Int3 mice. Thus, Notch-induced mammary tumor development is Rbpj-independent. Here, we show that Int3 activates NF-κB in HC11 cells in absence of Rbpj through an association with the IKK signalosome. Int3 induced the canonical NF-κB activity and P50 phosphorylation in HC11 cells without altering the NF-κB2 pathway. The minimal domain within the Int3 protein required to activate NF-κB consists of the CDC10/Ankyrin (ANK) repeats domain. Treatment of WAP-Int3 tumor bearing mice with an IKK inhibitor resulted in tumor regression. In a soft agar assay, treatment of HC11-Int3 cells with P50-siRNA caused a significant decrease in colony formation. In addition, Wap-Int3/P50 knockout mice did not develop mammary tumors. This data indicates that the activation of NF-κB canonical signaling by Notch-4/Int3 is ANK repeats dependent, Rbpj-independent, and is mediated by IKK activation and P50 phosphorylation causing mammary tumorigenesis.

Background and Aim: DNA methylation plays a critical role in the control of important cellular processes. The present study assessed the impact of promoter methylation (PM) of some genes on the antiviral response to antiviral therapy and it's relation to the presence of fibrosis in HCV-4 infected patients from Egypt., Material and Methods: Clinical, laboratory and histopathological data of 53 HCV-4 infected patients who were subjected to combined antiviral therapy were collected; patients were classified according to their response to treatment and the fibrosis status. The methylation profiles of the studied groups were determined using the following genes: APC, P14ARF, P73, DAPK, RASSF1A, and O6MGMT in patients' plasma., Results: O6MGMT and P73 showed the highest methylation frequencies (64.2 and 50.9%) while P14 showed the lowest frequency (34%). Sustained virological response (SVR) was 54.7%with no significant difference in clinico-pathological or laboratory features between the studied groups. PM of O6MGM was significantly higher in non-responders (p value 0.045) while DAPK showed high methylation levels in responders with no significance (p value: 0.09) andPM of RASSF1A was significantly related to mild fibrosis (p value: 0.019). No significant relations were reported between PM of any of the studied genes and patients' features., Conclusion: PM of some Tumor Suppressor genes increases in chronic active HCV-4. However, only 06MGMT can be used as a predictor of antiviral response and RASSF1A as a marker of marked fibrosis in this small set of patients. An extended study, including more patients is required to validate the results of this preliminary study.

The immortal strand theory postulates stem cells protect themselves from DNA replication-associated mutations and subsequent cancer risk through selective segregation of template DNA strands. Stem cells self-renew by asymmetric cellular division. During asymmetric division, stem cells maintain their template DNA strands, while the newly synthesized DNA strands segregate to newly formed daughter cells. Previous studies have demonstrated that self-renewing mammary stem cells originate in the expanding mammary ducts during puberty-associated allometric growth. In this study, we labeled newly forming mammary stem cells with the thymidine analog 5-ethynl-2'-deoxyuridine for 2 weeks during allometric ductal expansion. Cells that incorporate and retain the nuclear label following extended chase periods are termed label-retaining cells (LRCs). A second nuclear label, 5-bromodeoxyuridine, was administered before euthanasia to identify cells traversing the cell cycle. Mammary cells collected following euthanasia were sorted based on nuclear label retention. Members of the Notch and Wnt signaling pathways were found differentially expressed by mammary LRCs. These pathways are involved in the regulation of stem cells in the mouse mammary gland. Upon further analysis, we found that in contrast to non-LRCs, Notch1 and Notch2 are expressed and localized in the nuclei of the LRCs. Expression of Notch-inducible genes, Hes1 and Hey2, was elevated in LRCs. Inhibition of Notch1 by shRNA reduced colony forming potential and label retention by mammary epithelial cells in vitro. These results indicate that genes are differentially regulated in the LRC population of mammary glands and Notch1 mediates asymmetric cell division of mammary progenitor cells.

The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene expression in primary human breast tumors was interrogated. Twenty of the human orthologues of MMTV CIS associated genes are deregulated and/or mutated in human breast tumors.