Anti-proliferative and immunomodulatory potencies of cinnamon oil on Ehrlich ascites carcinoma bearing mice.

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.

A new approach for COVID-19 treatment by micro-RNA.

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.

Predictive value of haptoglobin genotype as a risk of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: This study aims to investigate the genetic predisposition of haptoglobin (Hp) genotype as a predictor for cerebral vasospasm (CV) after acute subarachnoid hemorrhage (aSAH) in the Egyptian population. This permits CV risk factors stratification of patients with aSAH. Hence, it will guide the treatment plan and intensive monitoring for those patients. PATIENTS AND METHODS: The study was carried out at El Matareya Teaching Hospital, Cairo, Egypt. We studied 50 patients with aSAH who were prospectively recruited and followed up by transcranial Doppler (TCD) examination for 14 days following aneurysmal rupture to early detect hemodynamic changes associated with CV and also the occurrence of delayed cerebral ischemia (DCI) as a secondary outcome. In this study, we attempted to analyze Hp genotyping as a potential predictor of CV and DCI during the acute phase of aneurysmal SAH. RESULTS: As a part of result analyses, among studied patients, 34 patients (68 %) developed CV and 19 patients (38 %) developed DCI. Only history of hypertension [RR = 1.6 (OR = 4)], diabetes mellitus [RR = 1.5 (OR = 3.4)] and smoking [RR = 1.5 (OR = 3.6)] had a significant independent relationship (P < 0.05) with short term risk to develop CV following aSAH. While, Age, sex, hyperlipidemia, cardiovascular disease and peripheral vascular disease, intracranial aneurysm site and size did not achieve significant association for developing CV. Regarding the poor Fisher scale and poor Hunt and Hess score both showed significant association with CV (P < 0.05). Genotyping of Hp protein among our study cohort revealed that the relative distribution of the three haptoglobin genotypes (Hp1-1, HP2-I & HP2-2) among Egyptian patients of aSAH was 14 %, 40 % and 46 %, respectively; (gene proportion being 0.34 for Hp1 and 0.66 for Hp2). Furthermore; Hp 2 allele was associated with radiographic vasospasm detected by TCD among the studied patients (2-2 & 2-1 Vs 1-1: RR = 5.4, OR = 19.8, P < 0.001). In the regression model; Hp genotype expressing Hp-2 allele is predictive for higher risk of development of CV after aSAH. Moreover, searching for the relationship between CV & Hp genotype and the risk for development of DCI; both variables failed to achieve a significant relationship for DCI (P > 0.05). CONCLUSION: The Hp genotype may determine the susceptibility to cerebral vasospasm after acute aSAH. This has the potential for use in risk stratification by allowing for the identification of those patients requiring intensive monitoring due to their inherent genetic risk for developing CV allowing for the promising selective application of aggressive treatments to those patients.

Anti-HBc and hepatitis B virus DNA among HBsAg-negative blood donors from the main central blood bank units in Eastern Libya.

BACKGROUND: Post-transfusion hepatitis B virus (PTHB) infection is still a public health problem in the world. In many developed countries, nucleic acid testing (NAT) for detection of Hepatitis B Virus (HBV)-DNA has been implemented to enhance blood donation safety. In Libya, however, the testing for HBV infection is limited to the detection of HBV surface antigen (HBsAg) only. OBJECTIVES: To determine the frequency of anti-Hepatitis B core antibody (HBc) and HBV-DNA in HBsAg-negative, anti-HBc-positive blood donors in the main Central Blood Bank Units (CBBUs) in eastern Libya. METHODS: One thousand blood samples were obtained from healthy blood donors at the five main CBBUs in eastern Libya. The samples were screened for HBsAg and anti-HBc. Real-time polymerase chain reaction (PCR) was carried out to detect HBV-DNA in all anti-HBc-positive samples. RESULTS: A total of 94 (9.4%) donors were positive for anti-HBc. Of the 94 anti-HBc-positive samples, 9 samples (9.5%) tested positive for HBV-DNA by real-time PCR. CONCLUSION: The rate of anti-HBc among blood donors in this study (9.4%) was similar to that reported from other regions in the country. In the absence of advanced tests for the detection of HBV infection in blood donors, such as NAT, anti-HBc should be routinely tested for, at least for first-time donors.

Dapagliflozin, a sodium glucose cotransporter 2 inhibitors, protects cardiovascular function in type-2 diabetic murine model.

Diabetes mellitus and its complications are major international health problems in which there are many limitations to the orthodox approaches in the treatment. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic medications, with a different mechanism of action that may reduce risk of cardiovascular complications. To evaluate the effect of SGLT2 inhibitor monotherapy on cardiovascular complications in patients with type-2 diabetes and to compare its effect with the first-line therapy, metformin. Eighty rats divided into four groups were used: nondiabetic, diabetic nontreated, diabetic + met and diabetic + dapa. At the end, the arterial blood pressure and cardiac performance were assessed. Glycemic index, lipid profile, total antioxidant capacity, malondialdehyde, tumour necrosis factor a were measured. DNA changes were assessed from the hearts and aortae. Aortic tissue changes recorded using haematoxylin and eosin, Masson trichrome and iNOS immune stain. Glycemic index, lipid profile, oxidative stress and inflammatory parameters were significantly improved in both metformin and dapagliflozin treated groups with significant improvement in blood pressure and cardiac performance. Also, there were noticeable significant reduction in DNA fragmentation in aortic and cardiac tissues and reduction in collagen deposition and iNOS expression in aortic tissue. Dapagliflozin treatment results' significantly surpassed improvement of metformin treatment nearly in all parameters. Total genomic DNA extraction proved that SGL2 inhibitor (dapagliflozin) has superior glycemic control and cardiovascular protective effect over metformin especially in type-2 diabetes with high fat intake.

Arg753Gln Polymorphisms in the Toll-Like Receptor 2 Gene are Associated with Cytomegalovirus Infection in Egyptian Bone Marrow Recipients.

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.

Triggering of apoptosis and cell cycle arrest by fennel and clove oils in Caco-2 cells: the role of combination.

Background: Fennel (Foeniculum vulgare) and clove (Syzygium aromaticum) oils are known for their various biological effects, including anticancer properties. Objective: To investigate the anticancer effect of combined fennel and clove oil treatment on Caco-2 cells and normal human lymphocytes (NHL). Methods: GC-MS, in vitro cytotoxicity, morphological, apoptosis-related marker, and flow cytometric cell cycle distribution analyses were conducted. Results: Seventeen volatile compounds were identified in fennel oil, including trans-anethole (68.3%) and (+)-fenchone (8.1%). In clove oil, 22 compounds, including eugenol (71.4%) and caryophyllene (8.7%), were identified. IC50 of the fennel, clove, and oil mixture were 300 ± 5.0, 150 ± 4.0, and 73 ± 2.5 µg/mL, respectively with combination index (CI) < 1.0. Mechanistic anticancer properties were investigated using 30, 45, and 60 µg/mL oil mixture. Analysis of apoptotic morphology, flow cytometric cell cycle distribution, and apoptosis-related markers, such as Bcl-2 and Ki-67, confirmed cell cycle arrest and apoptosis induction in Caco-2 cells by the fennel and clove oil combination. Moreover, the oil mixture did not exert significant (p < 0.01) toxicity on NHL in vitro. Conclusion: The oil mixture exerted selective cytotoxicity towards Caco-2 cells through cell cycle arrest and apoptosis, which may occur through synergistic effects between fennel and clove oil active ingredients.

Foeniculum Vulgare and Pelargonium Graveolens Essential Oil Mixture Triggers the Cell Cycle Arrest and Apoptosis in MCF-7 Cells.

BACKGROUND: Fennel (Foeniculum vulgare) and rose geranium (Pelargonium graveolens) oils are known for their various biological effects including anticancer properties. OBJECTIVE: This study aimed to evaluate the anticancer mechanism of fennel and geranium oils combined treatment on MCF-7 cells. METHODS: The GC-MS method for essential oil characterization as well as the in vitro cytotoxicity, morphological changes, real-time PCR and immunocytochemical investigation for apoptosis-related markers, in addition, to flow cytometric cell cycle distribution analysis were done. RESULTS: The major constituents of both essential oils were anethole (55.33 %) and estragole (11.57 %) for fennel essential oil. However, cintronellol (34.40 %) and geraniol (8.67 %) were identified in geranium oil. The results revealed an IC50 of 220±5.7 and 60±2.1µg/ml for fennel and geranium oils, respectively. The mechanistic anticancer properties were investigated throughout the 70, 50, and 25µg/ml of oils mixture. The marked apoptotic morphology and the flow cytometric cell cycle distribution analysis in addition to the levels of apoptosisrelated makers such as p53, caspase-3, mir-21, mir-92a, Bcl-2, and ki-67 confirmed that fennel and geranium oils combination induced cell cycle arrest and apoptosis in MCF-7 cells. Moreover, the oils mixture did not exert any significant (P<0.01) toxicity on normal human peripheral blood lymphocytes in vitro. CONCLUSION: The findings showed that the mixture of oils exerted selective cytotoxicity towards MCF-7 cells through induction of cell cycle arrest and apoptosis which may be triggered by the synergistic effect between the active ingredients of fennel and geranium oils.

HPLC Analysis of Phenolic Acids, Antioxidant Activity and in vitro Effectiveness of Green and Roasted Caffea arabica Bean Extracts: A Comparative Study.

BACKGROUND: 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. AIMS: 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). METHODS: 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). RESULTS: 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 GC and RC extract which showed slightly significant damage (P<0.001). 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.