myomiR-dependent switching of BAF60 variant incorporation into Brg1 chromatin remodeling complexes during embryo myogenesis.

Myogenesis involves the stable commitment of progenitor cells followed by the execution of myogenic differentiation, processes that are coordinated by myogenic regulatory factors, microRNAs and BAF chromatin remodeling complexes. BAF60a, BAF60b and BAF60c are structural subunits of the BAF complex that bind to the core ATPase Brg1 to provide functional specificity. BAF60c is essential for myogenesis; however, the mechanisms regulating the subunit composition of BAF/Brg1 complexes, in particular the incorporation of different BAF60 variants, are not understood. Here we reveal their dynamic expression during embryo myogenesis and uncover the concerted negative regulation of BAF60a and BAF60b by the muscle-specific microRNAs (myomiRs) miR-133 and miR-1/206 during somite differentiation. MicroRNA inhibition in chick embryos leads to increased BAF60a or BAF60b levels, a concomitant switch in BAF/Brg1 subunit composition and delayed myogenesis. The phenotypes are mimicked by sustained BAF60a or BAF60b expression and are rescued by morpholino knockdown of BAF60a or BAF60b. This suggests that myomiRs contribute to select BAF60c for incorporation into the Brg1 complex by specifically targeting the alternative variants BAF60a and BAF60b during embryo myogenesis, and reveals that interactions between tissue-specific non-coding RNAs and chromatin remodeling factors confer robustness to mesodermal lineage determination.

Klhl31 attenuates ß-catenin dependent Wnt signaling and regulates embryo myogenesis.

Klhl31 is a member of the Kelch-like family in vertebrates, which are characterized by an amino-terminal broad complex tram-track, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domain, carboxy-terminal Kelch repeats and a central linker region (Back domain). In developing somites Klhl31 is highly expressed in the myotome downstream of myogenic regulators (MRF), and it remains expressed in differentiated skeletal muscle. In vivo gain- and loss-of-function approaches in chick embryos reveal a role of Klhl31 in skeletal myogenesis. Targeted mis-expression of Klhl31 led to a reduced size of dermomyotome and myotome as indicated by detection of relevant myogenic markers, Pax3, Myf5, myogenin and myosin heavy chain (MF20). The knock-down of Klhl31 in developing somites, using antisense morpholinos (MO), led to an expansion of Pax3, Myf5, MyoD and myogenin expression domains and an increase in the number of mitotic cells in the dermomyotome and myotome. The mechanism underlying this phenotype was examined using complementary approaches, which show that Klhl31 interferes with ß-catenin dependent Wnt signaling. Klhl31 reduced the Wnt-mediated activation of a luciferase reporter in cultured cells. Furthermore, Klhl31 attenuated secondary axis formation in Xenopus embryos in response to Wnt1 or ß-catenin. Klhl31 mis-expression in the developing neural tube affected its dorso-ventral patterning and led to reduced dermomyotome and myotome size. Co-transfection of a Wnt3a expression vector with Klhl31 in somites or in the neural tube rescued the phenotype and restored the size of dermomyotome and myotome. Thus, Klhl31 is a novel modulator of canonical Wnt signaling, important for vertebrate myogenesis. We propose that Klhl31 acts in the myotome to support cell cycle withdrawal and differentiation.

Digestive Enzyme Activities, Oxidative Status and Intestinal Histomorphometry of Rats Supplemented with Steviana, A Natural Sweetener.

<b>Background and Objective:</b> Stevia (<i>Stevia rebaudiana</i>), often known as sweet leaf, is a perennial plant and a member of the Asteraceae family. The commercial version of stevia leaf powder, known as Steviana, is one of the most popular natural sweeteners in use today. The current study aimed to analyze the activities of gut digestive enzymes, intestinal oxidative state and intestinal histological structure in stevia-fed rats. <b>Materials and Methods:</b> In this study, male rats were given Steviana and the oxidative condition of the gastrointestinal tract (GIT), the activities of certain digestive enzymes and the histomorphology of the GIT were examined. Animals used in experiments were split into 2 groups: Control and treated groups. For four consecutive weeks, the treatment group received a daily oral intake of 5 mg kg¹ b.wt., of Steviana solution. At the end of the trial, serum, pancreas and intestinal tissue samples were taken. <b>Results:</b> The Steviana sweetener has a strong antioxidative effect on both blood and intestinal tissue. Both sample types showed a decrease in malondialdehyde levels and a marked increase in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities compared to control samples. In samples of blood, pancreas and intestinal contents, the activities of digestive enzymes including α-amylase, lipase and protease were significantly elevated in Steviana-treated rats. In addition, histological analysis of the small intestine showed that in rats given Steviana sweetener, intestinal glandular crypt depth was more pronounced compared to the control animals. <b>Conclusion:</b> In summary, consumption of Steviana appears to enhance digestion and absorption processes through antioxidative effects, improving the health of the local GIT and subsequently accelerating the rate of synthesis and release of endogenous digestive enzymes. Another aspect that enhances the digestion and absorption process is the change in the histological structure of the intestinal glands, as shown by an increase in the crypt depth.

Efficient Removal of Deltamethrin from Aqueous Solutions Using a Novel Lanthanum Metal-Organic Framework: Adsorption Models and Optimization via Box-Behnken Design.

Eliminating pesticides is essential for lowering the dangers to our environment. To do this effectively, it is crucial to find adsorbents with remarkable adsorption capacities, easy retrieval, and separation. Metal-organic frameworks (MOFs) have been extensively recognized for their exceptional ability to absorb pollutants. Therefore, we used novel lanthanum metal-organic frameworks (La-MOFs) to eliminate deltamethrin (DEL) from aqueous solutions. We proved through experimentation that the La-MOF is an efficient adsorbent for DEL from water. A study of the material revealed that the adsorbent had a surface area of 952.96 m2 per gram and a pore volume of 1.038 cm3/g. These outcomes show how this substance can absorb particles. Utilizing kinetic models and conforming to the pseudo-second-order model, a thorough analysis of the efficiency of DEL adsorption onto La-MOF was conducted. To create a perfectly tailored approach, we utilized many parameters. The synthetic La-MOF adsorbent may undergo up to five steps of adsorption-desorption and has exceptional cyclability and reusability. To confirm purifying wastewater samples in the laboratory, the presentation of the established adsorbent was evaluated. For the management of industrial effluent and water filtration, the La-MOF adsorbent offered a simple and effective solution. Our investigation suggests that the method we describe for removing DEL from wastewater samples using the La-MOF adsorbent is unique.

Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

The gyrfalcon (Falco rusticolus) genome.

High-quality genome assemblies are characterized by high-sequence contiguity, completeness, and a low error rate, thus providing the basis for a wide array of studies focusing on natural species ecology, conservation, evolution, and population genomics. To provide this valuable resource for conservation projects and comparative genomics studies on gyrfalcon (Falco rusticolus), we sequenced and assembled the genome of this species using third-generation sequencing strategies and optical maps. Here, we describe a highly contiguous and complete genome assembly comprising 20 scaffolds and 13 contigs with a total size of 1.193 Gbp, including 8,064 complete Benchmarking Universal Single-Copy Orthologs (BUSCOs) of the total 8,338 BUSCO groups present in the library aves_odb10. Of these BUSCO genes, 96.7% were complete, 96.1% were present as a single copy, and 0.6% were duplicated. Furthermore, 0.8% of BUSCO genes were fragmented and 2.5% (210) were missing. A de novo search for transposable elements (TEs) identified 5,716 TEs that masked 7.61% of the F. rusticolus genome assembly when combined with publicly available TE collections. Long interspersed nuclear elements, in particular, the element Chicken-repeat 1 (CR1), were the most abundant TEs in the F. rusticolus genome. A de novo first-pass gene annotation was performed using 293,349 PacBio Iso-Seq transcripts and 496,195 transcripts derived from the assembly of 42,429,525 Illumina PE RNA-seq reads. In all, 19,602 putative genes, of which 59.31% were functionally characterized and associated with Gene Ontology terms, were annotated. A comparison of the gyrfalcon genome assembly with the publicly available assemblies of the domestic chicken (Gallus gallus), zebra finch (Taeniopygia guttata), and hummingbird (Calypte anna) revealed several genome rearrangements. In particular, nine putative chromosome fusions were identified in the gyrfalcon genome assembly compared with those in the G. gallus genome assembly. This genome assembly, its annotation for TEs and genes, and the comparative analyses presented, complement and strength the base of high-quality genome assemblies and associated resources available for comparative studies focusing on the evolution, ecology, and conservation of Aves.

LRP6 Receptor Plays Essential Functions in Development and Human Diseases.

LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. It is required for the activation of the Wnt/ß-catenin signalling pathway. LRP6 is detected in different tissue types and is involved in numerous biological activities such as cell proliferation, specification, metastatic cancer, and embryonic development. LRP6 is essential for the proper development of different organs in vertebrates, such as Xenopus laevis, chickens, and mice. In human, LRP6 overexpression and mutations have been reported in multiple complex diseases including hypertension, atherosclerosis, and cancers. Clinical studies have shown that LRP6 is involved in various kinds of cancer, such as bladder and breast cancer. Therefore, in this review, we focus on the structure of LRP6 and its interactions with Wnt inhibitors (DKK1, SOST). We also discuss the expression of LRP6 in different model systems, with emphasis on its function in development and human diseases.

Editorial: Advances in genomic and genetic tools, and their applications for understanding embryonic development and human diseases.

Significant advances have been recently made in the development of the genetic and genomic platforms. This has greatly contributed to a better understanding of gene expression and regulation machinery. Consequently, this led to considerable progress in unraveling evidence of the genotype-phenotype correlation between normal/abnormal embryonic development and human disease complexity. For example, advanced genomic tools such as next-generation sequencing, and microarray-based CGH have substantially helped in the identification of gene and copy number variants associated with diseases as well as in the discovery of causal gene mutations. In addition, bioinformatic analysis tools of genome annotation and comparison have greatly aided in data analysis for the interpretation of the genetic variants at the individual level. This has unlocked potential possibilities for real advances toward new therapies in personalized medicine for the targeted treatment of human diseases. However, each of these genomic and bioinformatics tools has its limitations and hence further efforts are required to implement novel approaches to overcome these limitations. It could be possible that the use of more than one platform for genotype-phenotype deep analysis is an effective approach to disentangling the cause and treatment of the disease complexities. Our research topic aimed at deciphering these complexities by shedding some light on the recent applications of the basic and advanced genetic/genomic and bioinformatics approaches. These include studying gene-gene, protein-protein, and gene-environment interactions. We, in addition, aimed at a better understanding of the link between normal/abnormal embryonic development and the cause of human disease induction.

Genetic data sharing and artificial intelligence in the era of personalized medicine based on a cross-sectional analysis of the Saudi human genome program.

The success of the Saudi Human Genome Program (SHGP), one of the top ten genomic programs worldwide, is highly dependent on the Saudi population embracing the concept of participating in genetic testing. However, genetic data sharing and artificial intelligence (AI) in genomics are critical public issues in medical care and scientific research. The present study was aimed to examine the awareness, knowledge, and attitude of the Saudi society towards the SHGP, the sharing and privacy of genetic data resulting from the SHGP, and the role of AI in genetic data analysis and regulations. Results of a questionnaire survey with 804 respondents revealed moderate awareness and attitude towards the SHGP and minimal knowledge regarding its benefits and applications. Respondents demonstrated a low level of knowledge regarding the privacy of genetic data. A generally positive attitude was found towards the outcomes of the SHGP and genetic data sharing for medical and scientific research. The highest level of knowledge was detected regarding AI use in genetic data analysis and privacy regulation. We recommend that the SHGP's regulators launch awareness campaigns and educational programs to increase and improve public awareness and knowledge regarding the SHGP's benefits and applications. Furthermore, we propose a strategy for genetic data sharing which will facilitate genetic data sharing between institutions and advance Personalized Medicine in genetic diseases' diagnosis and treatment.

DISCOVID: discovering patterns of COVID-19 infection from recovered patients: a case study in Saudi Arabia.

A respiratory syndrome COVID-19 pandemic has become a serious global concern. Still, a large number of people have been daily infected worldwide. Discovering COVID-19 infection patterns is significant for health providers towards understanding the infection factors. Current COVID-19 research works have not been attempted to discover the infection patterns, yet. In this paper, we employ an Association Rules Apriori (ARA) algorithm to discover the infection patterns from COVID-19 recovered patients' data. A non-clinical COVID-19 dataset is introduced and analyzed. A sample of recovered patients' data is manually collected in Saudi Arabia. Our manual computation and experimental results show strong associative rules with high confidence scores among males, weight above 70 kilograms, height above 160 centimeters, and fever patterns. These patterns are the strongest infection patterns discovered from COVID-19 recovered patients' data.

Development of Thermochromic Ink Using the Anthocyanidin-Based Red-Cabbage Extract for Anticounterfeiting Applications.

Temperature-driven colorful switching inks have been an interesting security encoding method to improve the anticounterfeiting properties of commercially available merchandise. Recently, thermochromic inks have faced many disadvantages, such as low efficiency, high cost, and low durability. In the current study, we developed self-healable ink from poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPSA) integrated with the anthocyanidin(ACY)-based red-cabbage extract in the presence of ferrous sulfate for authentication purposes. Self-healable inks have been able to guarantee durability and thermal stability. Environmentally friendly, ACY-based chromophore was extracted from Brassica oleracea L. var. Capitata (red-cabbage) to serve as a spectroscopic probe immobilized into PAMPSA. The prepared self-healable nanocomposite ink (PAMPSA-ACY) displayed temperature-induced chromism with high reversibility and thermal stability. Different self-healable nanocomposite inks of thermochromic features were prepared employing different ratios of the ACY-based red-cabbage extract. As described by Commission Internationale de L'éclairage Lab coordinates, homogeneous films were stamped on the paper surface to show a purple color (631 nm) able to switch color into red (458 nm) with the increase in temperature from 25 to 65 °C, respectively. Transmission electron microscopy, infrared spectra (FT-IR), energy-dispersive X-ray, and scanning electron microscopy were utilized to inspect the morphological behavior and chemical compositions of thermochromic prints. Both mechanical and rheological properties of ink-printed paper substrates and ink solution were also investigated. Both of antimicrobial activity and cytotoxicity study of the nanocomposite ink (PAMPSA-ACY) were also evaluated. Various industries can take the advantage of the current ink as a competent approach for anticounterfeiting purposes.

Assessment of health awareness and knowledge toward SARS-CoV-2 and COVID-19 vaccines among residents of Makkah, Saudi Arabia.

INTRODUCTION: Public awareness regarding COVID-19 plays an important role in controlling the virus' spread and treating infected people. A high level of awareness among the public will help to implement preventive measures, particularly in the most populated regions, such as Makkah, Saudi Arabia. COVID-19 is an infectious disease and the Saudi Arabian government has taken serious precautions and implemented several preventive measures. In addition, The Ministry of Health (MOH) has launched many awareness campaigns and provided COVID-19 vaccines for free. THE OBJECTIVES: To assess the Public's level of health awareness and knowledge toward SARS-CoV-2 and COVID-19 vaccines among residents of Makkah, Saudi Arabia. METHODS: A cross-sectional study was conducted in the Makkah region from February 23 to March 2, 2021. The questionnaire was generated using a Google form and distributed online through social platforms such as Twitter and WhatsApp. The questionnaire consisted of five sections and six hundred participants have answered and completed all questions. Then, All data were imported into Microsoft Excel and analyzed using the statistical tools SAS version 9.4 and SPSS version 25 software. RESULTS: A total of 600 participants from the Makkah region were found to have a high level of awareness and knowledge about all aspects of SARS-CoV-2 and the COVID-19 disease. For example, all participants considered coronavirus to be contagious, and 89.8% of them knew that COVID-19's symptoms are similar to those of seasonal flu. Most respondents showed a high level of awareness regarding the main factors of SARS-CoV-2 transmission. Over 98.7% of respondents were aware of the role of gatherings and events in further spread of the virus. The participants showed a good level of awareness about other preventive measures, such as maintaining social distancing and wearing a mask. However, the respondents considered COVID-19 vaccines to be effective, but some of them were not aware of their side effects, and 38.8% planned to receive a vaccine. CONCLUSION: The residents of Makkah showed a high level of awareness about these aspects; an excellent awareness level was noted for SARS-CoV-2, means of transmission, disease symptoms and prevention of viral spread. On the other hand, the participants had less knowledge regarding COVID-19 vaccines; hence, more effort is required to educate people about the safety and benefits of the vaccines.

Synthesis and Self-assembly of Novel Nanofeather-like Fluorescent Alkyloxy-Containing Diphenyl Ether Organogelators.

In this study, novel fluorescent low molecular-weight organogelators are derived from diphenyl ethers and substituted with para-alkoxy groups of different aliphatic chain lengths. The present research promotes the preparation of innovative nanofeather-like assemblies from the synthesized diphenyl ether-derived organogelators. The gelation performance of the prepared alkoxy-substituted diphenyl ethers was reported. The synthesis procedure was achieved by using a base-catalyzed reaction of hydroxyl-substituted diphenyl with various alcohols of different aliphatic chain lengths. The chemical structures of the synthesized diphenyl ether derivatives were studied by 1H/13C NMR and infrared spectroscopy. Fluorescence and UV-vis absorption spectral analyses showed solvatochromism. The diphenyl ether derivatives with longer alkoxy terminal substituents showed enhanced thermoreversible gelation activity as compared to the diphenyl ether derivatives with shorter alkoxy terminal substituents. The morphological properties of the self-assembled diphenyl ethers were studied by transmission electron microscopy and scanning electron microscopy, which showed supramolecular architectures of highly ordered nanofeathers, enforced by van der Waals interactions and π-stacks. Depending on the length of the aliphatic tail, different morphologies were detected, including nanofeathers, nanofibers, and nanosheets. The antimicrobial and cytotoxic properties of the prepared diphenyl ether-derived organogelators were examined to confirm their possible use in various fields like drug delivery systems.

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach.

The diagnostic and prognostic utility of circulating cell-free DNA (cfDNA) in breast cancer (BC) patients was recently reported. Here, we investigated the use of cfDNA to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) for early BC diagnosis. cfDNA and genomic DNA from 41 female BC patients and 40 healthy controls were quantified using NanoDrop spectrophotometry and real-time PCR. The stability of genomic and cfDNA was assessed using a high-resolution AmpFlSTR MiniFiler human identification kit. Significant increases in cfDNA plasma concentrations were observed in BC patients compared to controls. The genotype distribution of the eight autosomal short tandem repeat (STR) loci D7S820, D13S317, D21S11, D2S1338, D18S51, D16S539, FGA, and CSF1PO were in Hardy-Weinberg equilibrium. Significant differences in the allele frequencies of D7S820 allele-8, D21S11 allele-29, allele-30.2, allele-32.2, and CSF1PO allele-11 were seen between BC patients and controls. LOH and MSI were detected in 36.6% of the cfDNA of patients compared to genomic DNA. This study highlights the utility of plasma-derived cfDNA for earlier, less invasive, and cost-effective cancer diagnosis and molecular stratification. It also highlights the potential value of cfDNA in molecular profiling and biomarkers discovery in precision and forensic medicine.

The Prognostic Value of the Developmental Gene FZD6 in Young Saudi Breast Cancer Patients: A Biomarkers Discovery and Cancer Inducers OncoScreen Approach.

Wnt signalling receptors, Frizzleds (FZDs), play a pivotal role in many cellular events during embryonic development and cancer. Female breast cancer (BC) is currently the worldwide leading incident cancer type that cause 1 in 6 cancer-related death. FZD receptors expression in cancer was shown to be associated with tumour development and patient outcomes including recurrence and survival. FZD6 received little attention for its role in BC and hence we analysed its expression pattern in a Saudi BC cohort to assess its prognostic potential and unravel the impacted signalling pathway. Paraffin blocks from approximately 405 randomly selected BC patients aged between 25 and 70 years old were processed for tissue microarray using an automated tissue arrayer and then subjected to FZD6 immunohistochemistry staining using the Ventana platform. Besides, Ingenuity Pathway Analysis (IPA) knowledgebase was used to decipher the upstream and downstream regulators of FZD6 in BC. TargetScan and miRabel target-prediction databases were used to identify the potential microRNA to regulate FZD6 expression in BC. Results showed that 60% of the BC samples had a low expression pattern while 40% showed a higher expression level. FZD6 expression analysis showed a significant correlation with tumour invasion (p < 0.05), and borderline significance with tumour grade (p = 0.07). FZD6 expression showed a highly significant association with the BC patients' survival outcomes. This was mainly due to the overall patients' cohort where tumours with FZD6 elevated expression showed higher recurrence rates (DFS, p < 0.0001, log-rank) and shorter survival times (DSS, p < 0.02, log-rank). Interestingly, the FZD6 prognostic value was more potent in younger BC patients as compared to those with late onset of the disease. TargetScan microRNA target-prediction analysis and validated by miRabel showed that FZD6 is a potential target for a considerable number of microRNAs expressed in BC. The current study demonstrates a potential prognostic role of FZD6 expression in young BC female patients and provides a better understanding of the involved molecular silencing machinery of the Wnt/FZD6 signalling. Our results should provide a better understanding of FZD6 role in BC by adding more knowledge that should help in BC prevention and theranostics.

Expression analysis of chick Frizzled receptors during spinal cord development.

Frizzleds (Fzds) are transmembrane receptors that can transduce signals dependent upon binding of Wnts, a large family of secreted glycoproteins homologous to the Drosophila wingless gene. FZDs are critical for a wide variety of normal and pathological developmental processes. In the nervous system, Wnts and Frizzleds play an important role in anterior-posterior patterning, cell fate decisions, proliferation, and synaptogenesis. Here, we preformed a comprehensive expression profile of Wnt receptors (FZD) by using situ hybridization to identify FZDs that are expressed in dorsal-ventral regions of the neural tube development. Our data show specific expression for FZD1,2,3,7,9 and 10 in the chick developing spinal cord. This expression profile of cFZD receptors offers the basis for functional studies in the future to determine roles for the different FZD receptors and their interactions with Wnts during dorsal-ventral neural tube development in vivo. Furthermore, we also show that co-overexpression of Wnt1/3a by in vivo electroporation affects FZD7/10 expression in the neural tube. This illustrates an example of Wnts-FZDs interactions during spinal cord neurogenesis.

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells.

Khat (Catha edulis (Vahl) Endl.) is an evergreen flowering shrub used as a stimulant in many regions worldwide including East Africa, the Arabian Peninsula, Europe, and the United States. Chewing leaves of khat induces excitement and euphoria, which are primarily attributed to two major constituents, cathinone and cathine. Khat also contains other important constituents such as cathedulins. A considerable number of studies reported side effects induced by the khat extracts to both embryos and adults. These include teratogenicity and developmental retardation, oral cancer and ulcers, high blood pressure, and myocardial infarction. So far, little attention has been paid to the effects of khat extracts on the molecular signaling interactions. We aimed in this study to investigate this through evaluating the effects of khat extracts on SKOV3, a human ovarian adenocarcinoma cell line. We show, by in vitro assays, that khat induces several cellular defects including reduced cell size, cell membrane damage, and apoptosis. At high khat extract concentrations, the cell metabolic activity, cell cycle, and cellular proliferation were affected. RT-qPCR analysis showed an increase in the gene expression of the apoptotic marker BAX, the tumor suppressor p53, and the inflammatory cytokine IL-6. Protein expression analysis by immunostaining showed downregulation of ß-catenin, E-cadherin, and Ki-67 and upregulation of FZD8 and SPRY2, suggesting that Wnt and FGF signaling were implicated. SwissTargetPrediction in silico analysis showed that khat constituents cathine, cathinone, catheduline K2, and catheduline E5 bind to family A G-protein-coupled receptor, cause many neurological diseases and disorders such as Alzheimer's, schizophrenia, depression, and anxiety, and induce many ovarian cancer-related diseases. The analysis also showed that important signaling pathways such as CREB, Wnt, FGF, IL-6, and ERK/MAPK, and that of the endometrial cancer, and cell cycle were implicated. Upstream regulators of cathine and cathinone were found to potentially target several molecules including interleukin-8, MMP2, PLAU, and micro-RNAs. In conclusion, khat induces significant cellular and molecular changes that could potentially cause a wide range of serious diseases and syndromes. Such an impact could have a heavy burden on the health care system in the countries where khat is consumed.

The Impact of Addition Oats (Avena sativa) and Cinnamon on Cookies and their Biological Effects on Rats Treated with Cirrhosis by CCL4.

Oats are represented an important source for nutrition, and it have attracted a lot of attention in recent years. In this study we produced oatmeal cookies and oats was added to formula wheat by 50% and 75%. Also, we added cinnamon to treatments 3 and 4 by 5% to increase nutrition value of oatmeal cookies, improvement sensory evaluation and increase antioxidant properties. All the cookies treatments were storage at room temperature. The purposes of this study were to study antioxidant activity for oats and cinnamon. Also determined the chemical composition include (moisture content, protein, ash, total lipids, crude fibers, carbohydrates and total calories) for oats, white flour and oatmeal cookies treatments. In addition evaluated all of sensory evaluation contain (appearance, color, texture, taste and odor) and microbiological evaluation such as (total bacterial count, spore forming bacteria and mold and yeasts count) for oatmeal cookies treatments. Also, biological assays were preformed to measure level of GPT, GOT, urea, creatinine, total cholesterol, triglycerides, HDL, LDL, and glucose. Furthermore, histopathological examination of both liver and kidneys was analyzed. The obtained results were clarified that the antioxidant activity for oats and cinnamon were 52.91% and 87.91%. Moreover, addition of oats and cinnamon to the cookies improve sensory evaluation as made it more acceptable, decreasing microbial load principally treatments 4 (prepared by 75% oats + 5% cinnamon). Biochemical assays were improved in rats with cirrhosis of carbon tetrachloride and their histopathological examination of liver and kidneys. It was clear that the additions ground whole grain oats and cinnamon to wheat flour based cookies improve its nutritional, chemical, and biological functions properties.

Molecular characterization of the Fe­hydrogenase gene marker in Trichomonas gallinae isolated from birds in Riyadh, Saudi Arabia.

Trichomonas gallinae causes avian oropharyngeal trichomonosis. This pathogen affects a large number of bird species and may cause substantial economic losses to the poultry industry. Al-Azizia poultry market in Riyadh, Saudi Arabia is among the largest poultry markets in the Arabian Gulf. Birds traded in this market may be exposed to a variety of T. gallinae strains. Genetic diversity of T. gallinae among birds in the market was examined using Fe­hydrogenase gene sequences. These sequences were amplified by PCR for twenty-nine isolates of T. gallinae from four different avian species, including 21 feral pigeons, one common mynah, three chickens, and four turkeys. Sequence analysis showed ten variant gene sequences. Nine sequences comprise a new subtype, including A(KSAF1), C(KSAF1) and C(KSAF3) with 34.48% (n = 10), 6.90% (n = 2), 6.90% (n = 2) of the isolates, respectively. Analyses also showed an additional five new sequences (KSAF1.1., KSAF2, KSAF13, KSAF14, KSAF15), representing 17.24% of the isolates. Subtype II (KSAF) was found in four feral pigeons (13.80%). To our knowledge, this report is the first to describe genotypes of T. gallinae from pigeons in Saudi Arabia using Fe­hydrogenase gene sequences for subtyping. Subtype analysis infers the presence of multiple genotypes of T. gallinae in Saudi avian populations.

FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord.

Wnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, ß -catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6.