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A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.

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Background: Metformin is a widely used anti-diabetic evaluated by several studies for its anti-cancer properties. However, the role of loaded metformin nanoparticles (NPs) in cancer therapy has not been investigated. This study addresses the cytotoxic effect of metformin and metformin cubosomes on Hct-116 and Caco-2 colorectal cancer (CRC) cell lines. Methods: Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of PluronicF-127 as a stabilizer. The loaded cubosomes were characterized in vitro. Design expert ® software was used for planning and analysis of the experimental trials to select the optimized formulation. Inhibitory effects of metformin cubosomes and the drug alone were investigated by Sulphorhodamine-B (SRB) assay. Results: The particle size, polydispersity index and zeta-potential were determined and revealed nanometer-sized particles with a narrow particle size distribution of 110-160 nm size and cubical morphology. Using the SRB assay, we demonstrate that drug-incorporated NPs induced significant toxicity on CRC cells compared to unloaded cubosomes or the drugs alone. Serial dilutions of empty cubosomes were added to both cell lines to determine their toxicity. Likewise, dilutions of metformin were tested and the concentration that inhibited 50% (IC50) of the cells was determined. The study revealed a decrease in the IC50 of metformin to 20 and 28mM in Caco-2 and Hct-116 cells after its formulation in cubosomes compared to 55 and 50mM of the drug alone respectively. Conclusions: These findings indicate that incorporation of low metformin concentrations in cubosomes profoundly increases its cytotoxic effect on colorectal cancer cells compared to the unformulated drug.

e49 lead to nephrotoxicity and ototoxicity. However, in SDD, tobramycin suspension is given orally and aminoglycosides are not absorbed via the gut. Therefore, SDD will, generally, not lead to systemic exposure. However, we describe a patient with Graft Versus Host Disease (GVHD) who developed toxic tobramycin levels. Methods: In this case report, we describe a 34 year old male patient with Acute Myeloid Leukemia. After allogenic stem cell transplantation he developed GVHD of the intestines, amongst all leading to severe diarrhea. Previously, several ICU patients with SDD and GVHD developed systemic tobramycin exposure. Therefore, tobramycin levels were measured by means of EMIT Immunoassay (Architect, Abbott). Results: After use of 8 times a day 80 mg tobramycin orally for 30 days, his tobramycin trough level was 3.5 mg/L (reference < 0.5 mg/L). His creatinine was 102 μ mol/L and urea was 23.1 mmol/L (increase > 20% last 4 days). Tobramycin was stopped and levels dropped to 0.87 mg/L after 2 days and 0.22 mg/L after 4 days. Tobramycin was started again in a regimen of 4 times a day 80 mg tobramycin orally, under daily monitoring of tobramycin levels. Creatinine and urea recovered. High tobramycin levels were contributed to systemic leakage of tobramycin via the intestines. Conclusion: In SDD, tobramycin is normally not absorbed. However, in severe intestine GVHD, systemic absorption of tobramycin can occur. In this patient toxic tobramycin levels were combined with impaired renal function. In patients with GVHD of the intestines and frequent administration of tobramycin-containing SDD frequent monitoring of tobramycin levels is recommended. Introduction: The link between inflammation and cancer has been suggested and confirmed by the use of anti-inflammatory therapies in cancer prevention and treatment. Five-aminosalicylic acid (5-ASA) was shown to decrease the growth and survival of colorectal cancer (CRC) cells. Metformin, an oral anti-diabetic drug, decreased the incidence of colorectal adenomas in diabetic patients with previous CRC and induced apoptosis in several cancer cell lines. This study addresses the combinatory effect of 5-ASA and Metformin and explores their role on oxidative stress markers, inflammatory mediators, as well as apoptosis on HCT-116 and Caco-2 CRC cell lines. Materials and Methods: Drug interaction was evaluated using isobologram equation and the expression of pro-inflammatory cytokines was determined by RT-PCR. Protein levels of BAX and Bcl-2 was determined using western blotting and matrix metalloproteinases-2 and -9 by zymography. Caspase-3 activity, malondialdehyde (MDA), glutathione (GSH) and nitric oxide contents were measured spectrophotometrically. Results: Metformin enhances CRC cell death induced by 5-ASA, this manifested a significant activation of apoptotic machinery, caspase-3 activity and the BAX/Bcl-2 protein ratio. In addition, the combination resulted in an exaggerated increase in MDA and decrease in intracellular GSH levels indicating an increase in oxidative stress ...