MicroRNAs (miRNAs) naturally occur in plants and all living organisms. They play an important role in gene regulation through binding toa specific region in open reading frames (ORFs) and/or untranslated regions (UTRs) to block the translation processes through either degrading or blocking mRNA resulting in knocking down or suppression of targeted genes. Plants and many organisms protect themselves from viruses through the production of miRNAs, which are complementary to 3UTR of viruses resulting in degrading the viral mRNA or block the translation on ribosomes. As pandemic, COVID-19, and its consequences on the global economy, we hypothesized a new approach for the treatment of COVID-19 paints. This approach includes designing a mix of miRNAs targeting several regions on COVID-19 open reading frame (ORF) and 3 UTR and suitable delivery system targeting respiratory system tissues. These synthesized miRNAs may be delivered to humansinnon-viral delivery systems such as liposomes like exosome (extracellular vesicle), polymer-based carriers, or inorganic nanoparticles, which are considered to be more suitable for human use.
Arabic gum (Acacia senegal, AG) is proven effective antioxidant and cytoprotective agent. The present study was designed to test this notion by investigating the possible role of AG against the radiographic contrast medium (Ioxitalamate, Telebrix-35®, TBX)-induced oxidative stress and genotoxicity. Albino rats were divided into four groups and supplied with either; distilled water, daily 10% (w/v) AG, an intravenous dose of TBX (1600 mg I/kg b.wt) and co-administration of TBX and AG. Rats were sacrificed and blood samples were collected to assess the genotoxicity employing the peripheral blood leucocytes fluorescent double staining; namely the acridine orange/ethidium bromide (AO/EB) staining and alkaline comet assay. Further, chromosomal analyses were done in bone marrow cells. Serum urea and creatinine levels, in addition to malondialdehyde (MDA), nitric oxide (NO), catalase (CAT) and glutathione (GSH) levels in kidney tissues were measured. Liquid chromatography-mass spectrophotometry (LC-MS-MS) was performed to identify the chemical composition of AG extract. Kidney functions, single/double-stranded DNA damage, chromosomal aberrations, mitotic index, MDA and NO levels were significantly (p < 0.001) increased in TBX-treated group compared to the control and AG-treated one. Meanwhile, CAT and GSH activities were significantly diminished and the AG supplementation significantly (p < 0.001) ameliorated these effects compared with the control and AG-treated groups. Five compounds have been identified using GNPS networking including 7,3′,4′-Trihydroxyisoflavone, Noscapine, Tetrahydropapaveroline, Costunolide, Hesperidin. In conclusion, results of the present study suggest that AG exerted a protective role against TBX-induced oxidative stress and genotoxicity which may be attributed to the active metabolites in the gum.
Cinnamon is a well-known natural spice and flavoring substance used worldwide. The objective of the present work is to explore the possible antitumor and immunomodulatory potencies of cinnamon essential oil (Cinn) on Ehrlich ascites carcinoma (EAC). A total of fifty female Swiss albino mice were sub-grouped into five groups (n = 10), namely, normal (a non-tumorized and non-treated) group; EAC-tumorized and non-treated group; Cinn (non-tumorized mice received Cinn, 50 mg/kg per body weight daily) group; a group of EAC-tumorized mice treated with Cinn and the final positive control group of EAC-tumorized mice received cisplatin. Eight compounds were identified from Cinn using UPLC-MS-Qtof and NMR analysis. Compared to EAC untreated group, Cinn successfully (P < 0.05) inhibited tumor growth by reducing tumor cell count (45%), viability (53%) and, proliferation accompanied by the inhibition of tumor growth rate. Moreover, a significant (P < 0.05) arrest in the cell cycle at G0/G1 phase was noticed following Cinn treatments (~ 24.5%) compared to EAC group. Moreover, Cinn markedly evoked an antitumor immune response by elevating the percentage of splenic T helper (CD3+CD4+) and T cytotoxic (CD3+CD8+) cells. It is noteworthy that Cinn treatments significantly restored different hematological alterations as well as liver and kidney functions in EAC-tumorized mice. In conclusion, results suggest that Cinn has a good antitumor and immunostimulatory potencies against Ehrlich ascites carcinoma in vivo. The mechanism underlying its antitumor activity may be attributed to its immunostimulatory effects which increase its potential as a promising anticancer candidate.
Background:: Vitamin C (VC) is believed to enhance immunity and is regularly integrated as a supplementary agent during several treatments. Objective:: The green (GC) and roasted (RC) coffee (Coffea arabica) aqueous extracts (0, 125, 250 and 500 μg/ml) combined with VC (50 μg/ml) were examined on the cancerous MCF-7 cell line and normal human lymphocytes. Methods:: Neutral red uptake assay, comet assay, immunocytochemical reactivity for protein expression and mRNA expression of apoptosis-related genes were performed. Results:: A significant (P< 0.05) concentration-dependent increase of apoptotic features, such as morphological changes, and abundant nuclear condensation, altered the expression of p53 and caspase-3 mRNA, down-regulation of Bcl-2 protein as well as the acidic autophagosomal vacuolization in treated cells. The oxidative stress and DNA single-strand breaks were noticed too. Conclusion:: These results suggest that coffee in combination with VC undergoes apoptotic anticancer pathway. This supports the integration of coffee and VC as a valuable candidate for anticancer research and treatments.
Coffee is a popular drink; it is one of the most commercialized food products and a rich source of biologically active compounds that are important for human health. This study aimed to prove the anticancer activity of green coffee (GC) and roasted coffee (RC) bean aqueous extracts (Coffea arabica) on breast cancer adenocarcinoma cell line (MCF-7) and the safety of both extracts on normal human peripheral blood lymphocytes culture (HPBL). Total phenolic content for GC and RC extracts was measured and result of both extracts were (0.308±0.016 & 0.233±0.013mg/g) respectively. The phenolic acids were screened by HPLC at the wavelength of 254& 278 and 300 nm and 5-caffeoylquinic acids (Chlorogenic acid), the predominant form of phenolic acids, was identified in GC and RC samples. Ferric reducing antioxidant power (FRAP) as well as the free radical scavenging activity (DPPH) proved the antioxidant properties of both extracts. The DPPH IC50 mean values of GC and RC extracts were (2.4±0.08, 2.3±0.16 μg/ml) respectively. Cytotoxicity of both extracts on MCF-7 cells were evaluated by neutral red uptake assay which showed the IC50 mean values (377±5.7,500±8.1 μg/ml) for GC and RC extracts respectively. The safety of both extracts (0, 125, 250, 500 μg/ml) on HPBL was evaluated in vitro using trypan blue exclusion method and DNA single strand breaks (alkaline comet assay). Result revealed non-significant cytotoxic difference (P<0.001) between cultures especially at lower doses of GC and RC extracts except the highest dose of BC and GC extract which showed slightly significant damage (P<0.001). In conclusion, this study proved that GC and RC aqueous extracts were found to be selectively cytotoxic in vitro to cancerous cells (MCF-7 cell line) causing cell death with no cytotoxicity on normal human lymphocytes especially at lower doses.
Background: Previous studies have shown that cytomegalovirus (CMV) induced innate immune response via activation of Toll-like receptor 2 (TLR2). The association between CMV among specific single-nucleotide polymorphisms (SNPs) in the TLR2 gene was also investigated. Objective: This study investigated the relationship between specific SNPs in the TLR2 gene (G>A), TLR2-Arg753Gln (rs5743708), and CMV replication after bone marrow transplantation. Methods: The TLR2-Arg753Gln SNP was genotyped in 181 patients after bone marrow transplantation: 83 and 98 patients with and without CMV infection, respectively. CMV load was determined in serially collected blood samples using real-time PCR. Genotyping was performed using specific sequence primer PCR (SSP-PCR), and the results were confirmed by restriction fragment length polymorphism (RFLP) analysis of the PCR-amplified fragments for GG (wild type), GA and AA identification. Results: Roughly, 85% of the patients screened for the presence of the TLR2-Arg753Gln were GG homozygous, and 15% were GA heterozygous; no patients were homozygous for the mutant allele (A). The GA heterozygous allele was more frequent in the CMV-infected group after bone marrow transplantation. Conclusion: To our knowledge, this is a novel observation that supports the notion that the functional missense mutation (TLR2-Arg753Gln polymorphism) is possibly associated with CMV replication after bone marrow transplantation. This suggests a role for TLR2 in the innate immune response of human CMV infection in Egyptian bone marrow recipients..
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