Two proteins comprising the ZEB family of zinc finger transcription factors, ZEB1 and ZEB2, execute EMT programs in embryonic development and cancer. By studying regulation of their expression, we describe a novel mechanism that limits ZEB2 protein synthesis. A protein motif located at the border of the SMAD-binding domain of ZEB2 protein induces ribosomal pausing and compromises protein synthesis. The function of this protein motif is dependent on stretches of rare codons, Leu(UUA)-Gly(GGU)-Val(GUA). Incorporation of these triplets in the homologous region of ZEB1 does not affect protein translation. Our data suggest that rare codons have a regulatory role only if they are present within appropriate protein structures. We speculate that pools of transfer RNA available for protein translation impact on the configuration of epithelial mesenchymal transition pathways in tumor cells.

Klebsiella aerogenes is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, which confer high resistance. The drug resistance in K. aerogenes has been reported in China, Israel, Poland, Italy and the United States, with a high mortality rate (~50%). This study aims to combine immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against K. aerogenes. The synthesis of the B-cell, T-cell (CTL and HTL) and IFN-γ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies. The vaccine was predicted by connecting the respective epitopes, i.e., B cells, CTL and HTL with KK, AAY and GPGPG linkers and all these were connected with N-terminal adjuvants with EAAAK linker. The humoral response of the constructed vaccine was measured through IFN-γ and B-cell epitopes. Before being used as vaccine candidate, all identified B-cell, HTL and CTL epitopes were tested for antigenicity, allergenicity and toxicity to check the safety profiles of our vaccine. To find out the compatibility of constructed vaccine with receptors, MHC-I, followed by MHC-II and TLR4 receptors, was docked with the vaccine. Lastly, in order to precisely certify the proper expression and integrity of our construct, in silico cloning was carried out. Further studies are needed to confirm the safety features and immunogenicity of the vaccine.

For the last few years, the world has been going through a difficult time, and the reason behind this is severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), one of the significant members of the Coronaviridae family. The major research groups have shifted their focus towards finding a vaccine and drugs against SARS-CoV-2 to reduce the infection rate and save the life of human beings. Even the WHO has permitted using certain vaccines for an emergency attempt to cut the infection curve down. However, the virus has a great sense of mutation, and the vaccine’s effectiveness remains questionable. No natural medicine is available at the community level to cure the patients for now. In this study, we have screened the vast library of experimental drugs of Drug Bank with Schrodinger’s maestro by using three algorithms: high-throughput virtual screening (HTVS), standard precision, and extra precise docking followed by Molecular Mechanics/Generalized Born Surface Area (MMGBSA). We have identified 3-(7-diaminomethyl-naphthalen-2-YL)-propionic acid ethyl ester and Thymidine-5′-thiophosphate as potent inhibitors against the SARS-CoV-2, and both drugs performed impeccably and showed stability during the 100 ns molecular dynamics simulation. Both of the drugs are among the category of small molecules and have an acceptable range of ADME properties. They can be used after their validation in in-vitro and in-vivo conditions.

Objective: The aim of this study was to examine the effect of some natural compounds against multidrug-resistant bacteria. Methods: Forty-three bacterial strains were collected. Disc diffusion and minimum inhibitory concentration (MIC) tests were carried out for natural compounds including quercetin, Acacia nilotica, Syzygium aromaticum, and Holothuria atra. Scanning electron microscope analysis and bacterial DNA apoptosis assays were performed. Results: Staphylococcus aureus strains were resistant to imipenim, ampicillin, and penicillin. Most Escherichia coli strains were resistant to amoxicillin, clavulanat, and ampicillin. Finally, tigecycline was effective with Klebsiella pneumoniae and was resistant to all antibiotics. Only S aromaticum had an antibacterial effect on K pneumoniae. Most S aureus strains were sensitive to S aromaticum, A nilotica, and quercetin. All examined natural extracts had no effect on E coli. Holothuria atra had no effect on any of the strains tested. Minimum inhibitory concentration and minimum bactericidal concentration values for examined plants against S aureus were 6.25 to 12, 1.6 to 3.2, and 9.12 to 18.24 mg/mL, respectively. Syzygium aromaticum was active against K pneumoniae with an MIC of 12.5 mg/mL. Scanning electron microscope analysis performed after 24 and 48 hours of incubation showed bacterial strains with distorted shapes and severe cell wall damage. Syzygium aromaticum, quercetin, and A nilotica showed clear fragmentations of S aureus DNA. Conclusions: Current findings confirmed the beneficial effect of using natural products such as clove (S aromaticum), quercetin, and A nilotica as a promising therapy to overcome multidrug resistant bacteria.