Beyond traditional medications: exploring novel and potential inhibitors of trypanothione reductase (LmTr) of Leishmania parasites.

The trypanothione reductase enzyme, which neutralizes the reactive oxygen species produced inside the macrophages to kill the parasites, is one of the evasion strategies Leishmania uses to survive inside the cells. The vitality of the parasite depends on Leishmania major trypanothione reductase (LmTr), a NADPH-dependent flavoprotein oxidoreductase essential for thiol metabolism. Since this enzyme is distinct and lacking in humans, we focused on it in our study to screen for new inhibitors to combat leishmaniasis. Using the I-TASSER server, a three-dimensional model of LmTr was generated. The Autodock vina program was used in high-throughput virtual screening of the ZINC database. The top seven molecules were ranked according to their binding affinity. The compounds with the highest binding affinities and the right number of hydrogen bonds were chosen. These compounds may be effective at inhibiting the target enzyme's (LmTr) activity, making them new leishmaniasis treatments. These compounds may serve as a useful starting point for a hit-to-lead approach in the quest for new anti-Leishmania drugs that are more efficient and less cytotoxic. The average node degree is 5.09, the average local clustering coefficient is 0.868, and the PPI enrichment p-value is 8.9e-06, indicating that it is sufficiently connected to regulate the network. TRYR (LmTr protein) also interacts physically with ten additional proteins in the pathogenesis network. The findings of the study indicated that successfully suppressing the LmTr protein in vitro and in vivo may finally result in regulating the L. major pathogenesis.Communicated by Ramaswamy H. Sarma.

Classification, processing, and applications of bioink and 3D bioprinting: A detailed review.

With the advancement in 3D bioprinting technology, cell culture methods can design 3D environments which are both, complex and physiologically relevant. The main component in 3D bioprinting, bioink, can be split into various categories depending on the criterion of categorization. Although the choice of bioink and bioprinting process will vary greatly depending on the application, general features such as material properties, biological interaction, gelation, and viscosity are always important to consider. The foundation of 3D bioprinting is the exact layer-by-layer implantation of biological elements, biochemicals, and living cells with the spatial control of the implantation of functional elements onto the biofabricated 3D structure. Three basic strategies underlie the 3D bioprinting process: autonomous self-assembly, micro tissue building blocks, and biomimicry or biomimetics. Tissue engineering can benefit from 3D bioprinting in many ways, but there are still numerous obstacles to overcome before functional tissues can be produced and used in clinical settings. A better comprehension of the physiological characteristics of bioink materials and a higher level of ability to reproduce the intricate biologically mimicked and physiologically relevant 3D structures would be a significant improvement for 3D bioprinting to overcome the limitations.

Development of highly-reproducible hydrogel based bioink for regeneration of skin-tissues via 3-D bioprinting technology.

3-D Bioprinting is employed as a novel approach in biofabrication to promote skin regeneration following chronic-wounds and injury. A novel bioink composed of carbohydrazide crosslinked {polyethylene oxide-co- Chitosan-co- poly(methylmethacrylic-acid)} (PEO-CS-PMMA) laden with Nicotinamide and human dermal fibroblast was successfully synthesized via Free radical-copolymerization at 73 °C. The developed bioink was characterized in term of swelling, structural-confirmation by solid state 13C-Nuclear Magnetic Resonance (NMR), morphology, thermal, 3-D Bioprinting via extrusion, rheological and interaction with DNA respectively. The predominant rate of gelation was attributed to the electrostatic interactions between cationic CS and anionic PMMA pendant groups. The morphology of developed bioink presented a porous architecture satisfying the cell and growth-factor viability across the barrier. The thermal analysis revealed two-step degradation with 85 % weight loss in term of decomposition and molecular changes in the bioink moieties By applying low pressure in the range of 25-50 kPa, the optimum reproducibility and printability were determined at 37 °C in the viscosity range of 500-550 Pa. s. A higher survival rate of 92 % was observed for (PEO-CS-PMMA) in comparison to 67 % for pure chitosan built bioink. A binding constant of K ≈ 1.8 × 106 M-1 recognized a thermodynamically stable interaction of (PEO-CS-PMMA) with the Salmon-DNA. Further, the addition of PEO (5.0 %) was addressed with better self-healing and printability to produce skin-tissue constructs to replace the infected skin in human.

Synthesis and evaluation of in vitro antiviral activity of novel phenoxy acetic acid derivatives.

Several substituted phenoxy acetic acid derived pyrazolines were synthesized by the reaction between 2-{4-[3-(2,4-dihydroxyphenyl)-3-oxo-1-propenyl]-2-methoxyphenoxy} acetic acid and substituted acid hydrazides and were tested for their in vitro cytotoxicity and antiviral activity. None of the compounds showed any specific antiviral activity [50% antivirally effective concentration (EC(50)) > or = 5-fold lower than minimum cytotoxic concentration]. The most cytotoxic of the series was 2-{4-[3-(2,4-dihydroxyphenyl)-1-(2-hydroxybenzoyl-4,5-dihydro-1H-5-pyrazolyl]-2-methoxyphenoxy}acetic acid (3(j)), with a minimum cytotoxic concentration of 0.16 microg/mL in human embryonic lung (HEL) cells.