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.

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.

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.

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.

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.

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.

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.

The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes as Immunomodulatory Agents for COVID-19 Patients.

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing lethal acute respiratory disease emerged in December 2019. The World Health Organization named this disease "COVID-19" and declared it a pandemic on March 11, 2020. Many studies have shown that mesenchymal stem cells (MSCs) and their exosomes (MSCs-Exo), which are isolated from allogenic bone marrow stem cells, significantly lower the risk of alveolar inflammation and other pathological conditions associated with distinct lung injuries. For example, in acute respiratory distress syndrome (ARDS) and pneumonia patients, MSCs-Exo and MSCs provide similar healing properties and some clinical trials have used cell-based inhalation therapy which show great promise. MSCs and MSCs-Exo have shown potential in clinical trials as a therapeutic tool for severely affected COVID-19 patients when compared to other cell-based therapies, which may face challenges like the cells' sticking to the respiratory tract epithelia during administration. However, the use of MSCs or MSCs-Exo for treating COVID-19 should strictly adhere to the appropriate manufacturing practices, quality control measurements, preclinical safety and efficacy data, and the proper ethical regulations. This review highlights the available clinical trials that support the therapeutic potential of MSCs or MSCs-Exo in severely affected COVID-19 patients.