Promoter Methylation-Regulated Differentially Expressed Genes in Breast Cancer.

Background: Breast cancer is one of the most common malignancies among women. Recent studies revealed that differentially methylated regions (DMRs) are implicated in regulating gene expression. The goal of this research was to determine which genes and pathways are dysregulated in breast cancer when their promoters are methylated in an abnormal way, leading to differential expression. Whole-genome bisulfite sequencing was applied to analyze DMRs for eight peripheral blood samples collected from five Saudi females diagnosed with stages I and II of breast cancer aligned with three normal females. Three of those patients and three normal samples were used to determine differentially expressed genes (DEG) using Illumina platform NovaSeq PE150. Results: Based on ontology (GO) and KEGG pathways, the analysis indicated that DMGs and DEG are closely related to associated processes, such as ubiquitin-protein transferase activity, ubiquitin-mediated proteolysis, and oxidative phosphorylation. The findings indicated a potentially significant association between global hypomethylation and breast cancer in Saudi patients. Our results revealed 81 differentially promoter-methylated and expressed genes. The most significant differentially methylated and expressed genes found in gene ontology (GO) are pumilio RNA binding family member 1 (PUM1) and zinc finger AN1-type containing 2B (ZFAND2B) also known as (AIRAPL). Conclusion: The essential outcomes of this study suggested that aberrant hypermethylation at crucial genes that have significant parts in the molecular pathways of breast cancer could be used as a potential prognostic biomarker for breast cancer.

Identification of novel interacts partners of ADAR1 enzyme mediating the oncogenic process in aggressive breast cancer.

Triple-negative breast cancer (TNBC) subtype is characterized by aggressive clinical behavior and poor prognosis patient outcomes. Here, we show that ADAR1 is more abundantly expressed in infiltrating breast cancer (BC) tumors than in benign tumors. Further, ADAR1 protein expression is higher in aggressive BC cells (MDA-MB-231). Moreover, we identify a novel interacting partners proteins list with ADAR1 in MDA-MB-231, using immunoprecipitation assay and mass spectrometry. Using iLoop, a protein-protein interaction prediction server based on structural features, five proteins with high iloop scores were discovered: Histone H2A.V, Kynureninase (KYNU), 40S ribosomal protein SA, Complement C4-A, and Nebulin (ranged between 0.6 and 0.8). In silico analysis showed that invasive ductal carcinomas had the highest level of KYNU gene expression than the other classifications (p < 0.0001). Moreover, KYNU mRNA expression was shown to be considerably higher in TNBC patients (p < 0.0001) and associated with poor patient outcomes with a high-risk value. Importantly, we found an interaction between ADAR1 and KYNU in the more aggressive BC cells. Altogether, these results propose a new ADAR-KYNU interaction as potential therapeutic targeted therapy in aggressive BC.

Construction of VSVΔ51M oncolytic virus expressing human interleukin-12.

The use of oncolytic viruses (OVs) in combination with cytokines, such as IL-12, is a promising approach for cancer treatment that addresses the limitations of current standard treatments and traditional cancer immunotherapies. IL-12, a proinflammatory cytokine, triggers intracellular signaling pathways that lead to increased apoptosis of tumor cells and enhanced antitumor activity of immune cells via IFN-γ induction, making this cytokine a promising candidate for cancer therapy. Targeted expression of IL-12 within tumors has been shown to play a crucial role in tumor eradication. The recent development of oncolytic viruses enables targeted delivery and expression of IL-12 at the tumor site, thereby addressing the systemic toxicities associated with traditional cancer therapy. In this study, we constructed an oncolytic virus, VSVΔ51M, based on the commercially available VSV wild-type backbone and further modified it to express human IL-12. Our preclinical data confirmed the safety and limited toxicity of the modified virus, VSV-Δ51M-hIL-12, supporting its potential use for clinical development.

Molecular Interaction Studies and Phytochemical Characterization of Mentha pulegium L. Constituents with Multiple Biological Utilities as Antioxidant, Antimicrobial, Anticancer and Anti-Hemolytic Agents.

Multiple biological functions of Mentha pulegium extract were evaluated in the current work. Phytochemical components of the M. pulegium extract were detected by Gas Chromatography-Mass Spectrometry (GC-MS) and High-performance liquid chromatography (HPLC). Moreover, M. pulegium extract was estimated for antioxidant potential by 2,2-Diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging, antimicrobial activity by well diffusion, and anticoagulant activity via prothrombin time (PT) and activated partial thromboplastin time (APTT). GC-MS analysis detected compounds including cholesterol margarate, stigmast-5-en-3-ol, 19-nor-4-androstenediol, androstan-17-one, pulegone-1,2-epoxide, isochiapin B, dotriacontane, hexadecanoic acid and neophytadiene. Chrysoeriol (15.36 µg/mL) was followed by kaempferol (11.14 µg/mL) and 7-OH flavone (10.14 µg/mL), catechin (4.11 µg/mL), hisperdin (3.05 µg/mL), and luteolin (2.36 µg/mL) were detected by HPLC as flavonoids, in addition to ferulic (13.19 µg/mL), cinnamic (12.69 µg/mL), caffeic (11.45 µg/mL), pyrogallol (9.36 µg/mL), p-coumaric (5.06 µg/mL) and salicylic (4.17 µg/mL) as phenolics. Antioxidant activity was detected with IC50 18 µg/mL, hemolysis inhibition was recorded as 79.8% at 1000 µg/mL, and PT and APTT were at 21.5 s and 49.5 s, respectively, at 50 µg/mL of M. pulegium extract. The acute toxicity of M. pulegium extract was recorded against PC3 (IC50 97.99 µg/mL) and MCF7 (IC50 80.21 µg/mL). Antimicrobial activity of M. pulegium extract was documented against Bacillus subtilis, Escherichia coli, Pseudomonasaureus, Candida albicans, Pseudomonas aeruginosa, but not against black fungus Mucor circinelloides. Molecular docking was applied using MOE (Molecular Operating Environment) to explain the biological activity of neophytadiene, luteolin, chrysoeriol and kaempferol. These compounds could be suitable for the development of novel pharmacological agents for treatment of cancer and bacterial infections.

DNA Methylation Level of Transcription Factor Binding Site in the Promoter Region of Acyl-CoA Synthetase Family Member 3 (ACSF3) in Saudi Autistic Children.

BACKGROUND: DNA methylation (DNAm) is one of the main epigenetic mechanisms that affects gene expression without changing the underlying DNA sequence. Aberrant DNAm has an implication in different human diseases such as cancer, schizophrenia, and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that affects behavior, learning, and communication skills. Acyl-CoA synthetase family member 3 (ACSF3) encodes malonyl-CoA synthetase that is involved in the synthesis and oxidation of fatty acids. The dysregulation in such gene has been reported in combined malonic and methylmalonic aciduria associated with neurological symptoms such as memory problems, psychiatric diseases, and/or cognitive decline. This research aims to study DNAm in the transcription factor (TF) binding site of ACSF3 in Saudi autistic children. To determine whether the DNAm of the TF-binding site is a cause or a consequence of transcription regulation of ACSF3. METHODS: RT-qPCR and DNA methylight qPCR were used to determine the expression and DNAm level in the promoter region of ACSF3, respectively. DNA and RNA were extracted from 19 cases of ASD children and 18 control samples from their healthy siblings. RESULTS: The results showed a significant correlation between the gene expression of ACSF3 and specificity protein 1 (SP1) in 17 samples of ASD patients, where both genes were upregulated in 9 samples and downregulated in 8 samples. CONCLUSION: Although this study found no DNAm in the binding site of SP1 within the ACSF3 promoter, the indicated correlation highlights a possible role of ACSF3 and SP1 in ASD patients.

Anticancer potential of ascorbic acid and inorganic selenium on human breast cancer cell line MCF-7 and colon carcinoma HCT-116.

BACKGROUND AND OBJECTIVES: Till now, cancer is a major health problem and one of the main causes of mortality worldwide. Ascorbic acid and selenium are the two most popular dietary supplements used to prevent cancer proliferative, therefore, the work aims to study the antitumor effect of ascorbic acid and selenium on HCT116 and MCF7 cell lines. MATERIALS AND METHODS: In the present study, the cytotoxic effect of different concentrations of ascorbic acid and selenium on human breast cancer cell line (MCF7 cells) and human colon carcinoma (HCT116) was studied. RESULTS: Viability % of HCT116 cell line and MCF7 cell line decreased with increasing ascorbic acid concentrations (1-4 mM). The 50% inhibitory concentration (IC50) of five dilutions of each concentration of ascorbic acid was evaluated in the current study. IC50 was 0.18, 0.17, 0.16, and 0.16 mM for HCT116 cell line and was 0.86, 1.34, 1.74, and 0.47 mM for MCF7 cell line at 1, 2, 3, and 4 mM, respectively. Cell viability decreased depending on the selenium concentrations ranging from 20 to 100 mM. Selenium effect showed less cytotoxicity on MCF7 compared to HCT116 cells at all tested concentrations where the cell viability at 20, 40, 60, 80, and 100 mM selenium was 33.74, 29.48, 26.08, 54.53, and 20.89 for HCT116 cell and was 79.53, 76.01, 59.42, 54.53, and 51.98 for MCF7 cell, respectively. Ascorbic acid induced apoptosis by promoting the release of lactate dehydrogenase (LDH) in HCT116 and MCF7 cells, but reduced release of LDH was observed in selenium treatment but increased when it added to ascorbic acid because of a possible synergistic action that may produce an enhanced anticarcinogenic effect. CONCLUSION: The present study documented that a combination of ascorbic acid and selenium produces an additive chemopreventive effect on carcinogenesis.

Protein modeling, molecular network and molecular dynamics study of newly sequenced interleukin-18 (IL-18) gene in Mus musculus.

Interleukin-18 (IL-18) belongs to the superfamily of IL-1 protein and exerts a pleiotropic pro-inflammatory effect on the body. Generally, this protein is significantly involved in immune defense during infection in cells, but sometimes its anomalous activities produce some inflammatory diseases like rheumatoid arthritis and Crohn's disease. In the present study, the IL-18 gene was isolated from mice and was subsequently cloned and sequenced. Further, the network analysis was carried out to explore the functional role of IL-18 protein in animals. The 3D protein structure of the IL-18 protein was generated and docked with appropriate 3-([3-cholamidopropyl]dimethylammonio)-1-propanesulfonate (CPS) ligand. Later the complex structure of the protein was subjected to molecular dynamics simulation (MDS) for 50 ns to determine the effect of ligand on protein. The network analysis explored the correlation of IL-18 protein with others proteins and their involvement in the different significant pathway to defend the cell from various diseases. As confirmed by MDS, the CPS:IL-18 complex was found to be highly stable. Our results further indicated that CPS ligand has the potential to act as a drug molecule, in future, for counteracting IL-18 activity. To date, no structural details were available for animal IL-18. Hence, the finding of this study will be useful in broadening the horizon towards a better understanding of the functional and structural aspects of IL-18 in animals.

Essential Oils: Extraction Techniques, Pharmaceutical And Therapeutic Potential - A Review.

BACKGROUND: Essential oils are liquid extracts from aromatic plants, which have numerous applications in multiple industries. There are a variety of methods used for the extraction of essential oils, with each method exhibiting certain advantages and determining the biological and physicochemical properties of the extracted oils. Essential oils from different plant species contain more than 200 constituents which are comprised of volatile and non-volatile components. The application of essential oils as antimicrobial, anticancer, anti-inflammatory and anti-viral agents is due to their effective and efficient properties, inter alia. METHOD: Several advanced (supercritical fluid extraction, subcritical extraction liquid, solvent-free microwave extraction) and conventional (hydrodistillation, steam distillation, hydrodiffusion, solvent extraction) methods have been discussed for the extraction of essential oils. Advanced methods are considered as the most promising extraction techniques due to less extraction time, low energy consumption, low solvent used and less carbon dioxide emission. CONCLUSION: This manuscript reviewed the major research studies in the field and discussed several research findings on the chemical composition of essential oils, methods of oil extraction, and application of these oils in pharmaceutical and therapeutic fields. These essential oils can be used as anticancer, antimicrobial, antiviral, and as skin permeation enhancer agents.

Frontier View on Nanotechnological Strategies for Neuro-therapy.

BACKGROUND: Nanotechnology exploits materials and devices with a functional organization that has been engineered at the nanometre scale. The application of nanotechnology in neuroscience involves specific interactions with neurons and glial cells. This property is used for delivering drugs and other small molecules (such as genes, oligonucleotides and contrasting agents) across the blood brain barrier (BBB), an important requirement for delivering the drug successfully to the brain. OBJECTIVE: Nanotechnology based approaches (NBA) favours transcytosis-mediated delivery of nanoparticles to the brain by crossing the BBB. The last five years have witnessed the successful applications of NBA to treat neurological disorders. It is expected that the development of novel NBA will result in important insights on the brain mechanisms, and eventually provide better medical care to patients suffering from neurological disorders. CONCLUSION: This review introduces the emerging work in this area and summarizes the successful NBA used in recent past for treating various neurological disorders ike Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, meningitis and glioblastoma.

Potentiating Effect of Ethnomedicinal Plants Against Proliferation on Different Cancer Cell Lines.

BACKGROUND: There is a long history of traditional medicine for serving the world population. For the prevention and treatment of cancer, herbal remedies have played a significant role. In this review, we have summarized medicinal herbs from the entire world, including India, that are used traditionally for various cancer treatment. Whenever we talk about cancer treatment, medicinal plants always have been on the priority. OBJECTIVE: In this article, we have summarized the flora used in earlier times and recently identified for pre-clinical anticancer treatment. The present paper is a comprehensive review of different literature sources with discussion being made on the therapeutic value of diverse medicinal herbs in the treatment of various kinds of cancer by using different in vitro cancer cell lines. Countless anticancer plants have been recognized with the help of innovative techniques including isolation and structure elucidation that implement their beneficial effect by increasing the immunity of the body, inducing antioxidant action, endorsing making of shielding enzymes, hindering cancer triggering enzymes and hormones, and exciting DNA restoration mechanism. CONCLUSION: Finally, we have concluded that Argemone mexicana shows maximum anti-cancer activity on various cancer cell lines in comparison to other medicinal plants.

PeMtb: A Database of MHC Antigenic Peptide of Mycobacterium tuberculosis.

BACKGROUND: For design of a subunit vaccine for tuberculosis, identification of antigenic Tcell epitope is of utmost importance. Several MHC prediction server are available that can accurately predict antigenic peptide of variable lengths. However, peptides predicted from one server not necessarily are predicted form another server, thus creating a confusing situation for scientists to choose a best epitope. METHOD: Keeping the above problem in mind, we developed a comprehensive database of peptides of Mycobacterial proteins. Each protein was taken from PubMed and was run through different MHC prediction servers, with the results being compiled into one database. RESULTS: For each protein, PeMtb generates a set of three different mers of variable lengths (12 mer or 13-mer) based on their ranking; with each mer being predicted for a plethora of MHC alleles. Researcher can choose the peptide (mers) that gives best binding affinity from most of the servers. CONCLUSION: The database relieves the investigators of the painstaking task of searching various MHC prediction servers for the right epitope (T-cell epitope) for a particular Mycobacterial antigen. We trust and anticipate that PeMtb will be a practical platform for trial and computational analyses of antigenic peptides for Mycobacterium tuberculosis. All the resources and information can be accessed by PeMtb home page www.pemtb-amu.org.