Coronary Artery Bypass Grafting: Surgical Anastomosis: Tips and Tricks

The definite feature of coronary artery disease is the focal narrowing in the vascular endothelium, and this leads to the decrease in the flow of blood to the myocardium. Atherosclerotic plaque is the main lesion. These patients can present with chest pain (angina or myocardial infarction) and need further workup noninvasively and invasively for the management. The main reasons for myocardial revascularization can be: (1) relief from symptoms of myocardial ischemia; (2) reduce the risks of future mortality; (3) to treat or prevent morbidities such as myocardial infarction, arrhythmias, or heart failure. Coronary artery bypass grafting (CABG) is the surgical technique of cardiac revascularization. In 1910, Dr. Alexis Carrel described a series of canine experiments in which he devised means to treat CAD by creating a “complementary circulation” for the diseased native coronary arteries. No clinical translation occurred at the time, but he was awarded the Nobel Prize in Medicine. Experimental refinements of coronary arterial revascularization, including the use of internal thoracic artery (ITA) grafts, were later reported by Murray and colleagues, Demikhov, and Goetz and colleagues in the 1950s and early 1960s. Dr. Rene Favaloro performed his first coronary bypass operation in May 1967 with an interposed saphenous vein graft (SVG) and shortly thereafter used aortocoronary bypasses sutured proximally to the ascending aorta. The stenosed segment is bypassed using an arterial or venous graft. Left internal thoracic artery is the most commonly used artery, and long saphenous vein is the most commonly used vein for the coronary artery grafting to reestablish the blood flow to the compromised myocardium. This can be performed with or without the help of cardiopulmonary bypass machine and also with or without arresting the heart. These techniques are called as on-pump beating or on-pump arrested and off-pump beating coronary artery bypass grafting surgery. Distal and proximal anastomoses are usually performed in an end-to-side manner, but in the case of doing sequential grafting, side-to-side anastomosis is also performed proximal to the end-to-side anastomosis. In this chapter we are going to discuss the coronary artery bypass grafting tips and tricks in details

Different Sites of Vascular Access for Transcutaneous Aortic Valve Implantation (TAVI)

Aortic valve stenosis is a common valvular heart disease and its incidence is increasing day by day as the life expectancy is increasing gradually. It can be of congenital or acquired variety but in old ages aortic stenosis is acquired mostly and main reasons rheumatic heart disease or senile calcification of aortic valve. Aortic valve replacement with mechanical tissue valves is the surgical management of aortic valve stenosis but some of the patients are not suitable for the surgery based on their physical status and associated comorbidities. These patients are high risk for surgical complications or they have prohibitive risks for surgery. Transcutaneous aortic valve implantation is the new technique developed to implanting aortic valve mostly without opening the sternum and without using cardiopulmonary bypass machine. This procedure is mostly done via transfemoral access but in case of contraindications to use femoral artery for access some other different accesses are used to implant the aortic valve, that is, transsubclavian/transaxillary access, transapical access, transaortic access, transcarotid and transcaval accesses. In this chapter we are going to discuss all accesses in details

Inhibiting CDK6 activity by quercetin is an attractive strategy for cancer therapy

Cyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed in silico and in vitro screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC50 = 5.89 μM. Molecular docking and a 200 ns whole atom simulation of the CDK6-quercetin complex provide insights into the binding mechanism and stability of the complex. Binding parameters ascertained by fluorescence and isothermal titration calorimetry studies revealed a binding constant in the range of 107 M−1 of quercetin to the CDK6. Thermodynamic parameters associated with the formation of the CDK6−quercetin complex suggested an electrostatic interaction-driven process. The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6. Quercetin also decreases the viability and colony formation potential of selected cancer cells. Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression. Both in silico and in vitro studies highlight the significance of quercetin for the development of anticancer leads in terms of CDK6 inhibitors

Antennal enriched odorant binding proteins are required for odor communication in glossina f. Fuscipes

Olfaction is orchestrated at different stages and involves various proteins at each step. For example, odorant-binding proteins (OBPs) are soluble proteins found in sensillum lymph that might encounter odorants before reaching the odorant receptors. In tsetse flies, the function of OBPs in olfaction is less understood. Here, we investigated the role of OBPs in Glossina fuscipes fuscipes olfaction, the main vector of sleeping sickness, using multidisciplinary approaches. Our tissue expression study demonstrated that GffLush was conserved in legs and antenna in both sexes, whereas GffObp44 and GffObp69 were expressed in the legs but absent in the antenna. GffObp99 was absent in the female antenna but expressed in the male antenna. Short odorant exposure induced a fast alteration in the transcription of OBP genes. Furthermore, we successfully silenced a specific OBP expressed in the antenna via dsRNAi feeding to decipher its function

In silico repurposing of a Novobiocin derivative for activity against latency associated Mycobacterium tuberculosis drug target nicotinate-nucleotide adenylyl transferase (Rv2421c)

Nicotinamide-nucleotide adenylyl transferase (Rv2421c) was selected as a potential drug target, because it has been shown, in vitro, to be essential for Mycobacterium tuberculosis growth. It is conserved between mycobacterium species, is up-regulated during dormancy, has a known 3D crystal structure and has no known human homologs. A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject tovirtual ligand screening against the Prestwick Chemical Library and the ZINC database, which yielded 155 potential hit molecules. Of the 155 compounds identified five were pursued further using an IC50 based 3D-QSAR study. The 3D-QSAR model validated the inhibition properties of the five compounds based on R2 value of 0.895 and Q2 value of 0.944 compared to known inhibitors of Rv2421c. Higher binding affinities was observed for the novel ZINC13544129 and two FDA approved compounds (Novobiocin sodium salt, Sulfasalazine). Similarly, the total interaction energy was found to be the highest for Cromolyn disodium system (-418.88 kJ/mol) followed by Novobiocin (-379.19 kJ/mol) and Sulfasalazine with (-330.13 kJ/mol) compared to substrate DND having (-185.52 kJ/mol). Subsequent in vitro testing of the five compounds identified Novobiocin sodium salt with activity against Mycobacterium tuberculosis at 50 μM, 25μM and weakly at 10μM concentrations. Novobiocin salt interacts with a MG ion and active site residues His20, Thr86, Gly107 and Leu164 similar to substrate DND of Mycobacterium tuberculosis Rv2421c. Additional in silico structural analysis of known Novobiocin sodium salt derivatives against Rv2421c suggest Coumermycin as a promising alternative for the treatment of Mycobacterium tuberculosis based on large number of hydrogen bond interactions with Rv2421c similar in comparison to Novobiocin salt and substrate DND

Cellular and molecular targets of waterbuck repellent blend odors in antennae of glossina fuscipes fuscipes newstead, 1910

Insects that transmit many of the world’s deadliest animal diseases, for instance trypanosomosis, find their suitable hosts and avoid non-preferred hosts mostly through olfactory cues. The waterbuck repellent blend (WRB) comprising geranylacetone, guaiacol, pentanoic acid, and d-octalactone derived from waterbuck skin odor is a repellent to some savannah-adapted tsetse flies and reduces trap catches of riverine species. However, the cellular and molecular mechanisms associated with detection and coding of the repellent odors remain to be elucidated. Here, we demonstrated that WRB inhibited blood feeding in both Glossina pallidipes Austen, 1903 and Glossina fuscipes fuscipes Newstead, 1910. Using the DREAM (Deorphanization of Receptors based on Expression Alterations in odorant receptor mRNA levels) technique, combined with ortholog comparison and molecular docking, we predicted the putative odorant receptors (ORs) for the WRB in G. f. fuscipes, a non-model insect

Corrigendum: Synthesis and cytotoxic activity of novel indole derivatives and their in silico screening on spike glycoprotein of sars-cov-2

The authors Kaliappillai Vijayakumar, Magda H. Abdellattif, Mohd Shahbaaz were not included in the published article and the authors Daoud Ali, Saud Alarifi, and Amal Alotaibi were mistakenly included in the author list. The author list has been corrected throughout the article and in the Author Contributions statement. In addition, the funding information was incorrect and has been amended to include funding for Magda H. Abdellattif. The corrected Author Contributions, Funding and Acknowledgments statements appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Designing novel possible kinase inhibitor derivatives as therapeutics against Mycobacterium tuberculosis: An in silico study

Rv2984 is one of the polyphosphate kinases present in Mycobacterium tuberculosis involved in the catalytic synthesis of inorganic polyphosphate, which plays an essential role in bacterial virulence and drug resistance. Consequently, the structure of Rv2984 was investigated and an 18 membered compound library was designed by altering the scaffolds of computationally identified inhibitors. The virtual screening of these altered inhibitors was performed against Rv2984 and the top three scoring inhibitors were selected, exhibiting the free energy of binding between 8.2–9 kcal mol−1 and inhibition constants in the range of 255–866 nM. These selected molecules showed relatively higher binding affinities against Rv2984 compared to the first line drugs Isoniazid and Rifampicin. Furthermore, the docked complexes were further analyzed in explicit water conditions using 100 ns Molecular Dynamics simulations. Through the assessment of obtained trajectories, the interactions between the protein and selected inhibitors including first line drugs were evaluated using MM/PBSA technique. The results validated the higher efficiency of the designed molecules compared to 1st line drugs with total interaction energies observed between −100 kJ mol−1 and −1000 kJ mol−1. This study will facilitate the process of drug designing against M. tuberculosis and can be used in the development of potential therapeutics against drug-resistant strains of bacteria

Repurposing based identification of novel inhibitors against mmps5-mmpl5 efflux pump of Mycobacterium smegmatis: A combined in silico and in vitro study

In the current era of a pandemic, infections of COVID-19 and Tuberculosis (TB) enhance the detrimental effects of both diseases in suffering individuals. The resistance mechanisms evolving in Mycobacterium tuberculosis are limiting the efficiency of current therapeutic measures and pressurizing the stressed medical infrastructures. The bacterial efflux pumps enable the development of resistance against recently approved drugs such as bedaquiline and clofazimine. Consequently, the MmpS5-MmpL5 protein system was selected because of its role in efflux pumping of anti-TB drugs. The MmpS5-MmpL5 systems of Mycobacterium smegmatis were modelled and the virtual screening was performed using an ASINEX library of 5968 anti-bacterial compounds. The inhibitors with the highest binding affinities and QSAR based highest predicted inhibitory concentration were selected. The MmpS5-MmpL5 associated systems with BDE_26593610 and BDD_27860195 showed highest inhibitory parameters

Oxazinethione derivatives as a precursor to pyrazolone and pyrimidine derivatives: Synthesis, biological activities, molecular modeling, adme, and molecular dynamics studies

The authors thank Taif University Researchers, supporting project number TURSP-2020/91, Taif University, Taif, Saudi Arabia.In this study, we used oxazinethione as a perfect precursor to synthesize new pyrimidine and pyrazole derivatives with potent biological activities. Biological activities were determined for all compounds against A. flavus, E. coli, S. aureus, and F. moniliform. Compounds 3, 4a-b, and 5 exhibited higher activities toward A. flavus, E. coli, S. aureus, and F. moniliform; this was indicated through the MIC (minimum inhibitory concentration). At the same time, anticancer activities were determined through four cell lines, Ovcar-3, Hela, MCF-7, and LCC-MMk. The results obtained indicated that compound 5 was the most potent compound for both cell lines. Molecular docking was studied by the MOE (molecular operating environment). The in silico ADME of compounds 2 and 5 showed good pharmacokinetic properties. The present research strengthens the applicability of these compounds as encouraging anticancer and antibacterial drugs. Moreover, JAGUAR module MD simulations were carried out at about 100 ns. In addition, spectroscopic studies were carried out to establish the reactions of the synthesized structure derivatives. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Taif University Researchers: TURSP-2020/91 Taif Universit