Unraveling the versatility of human serum albumin - A comprehensive review of its biological significance and therapeutic potential.

Human serum albumin (HSA) is a multi-domain macromolecule with diverse ligand binding capability because of its ability to allow allosteric modulation despite being a monomeric protein. Physiologically, HSA act as the primary carrier for various exogenous and endogenous compounds and fatty acids, and alter the pharmacokinetic properties of several drugs. It has antioxidant properties and is utilized therapeutically to improve the drug delivery of pharmacological agents for the treatment of several disorders. The flexibility of albumin in holding various types of drugs coupled with a variety of modifications makes this protein a versatile drug carrier with incalculable potential in therapeutics. This review provides a brief outline of the different structural properties of HSA, and its various binding sites, moreover, an overview of the genetic, biomedical, and allosteric modulation of drugs and drug delivery aspects of HSA is also included, which may be helpful in guiding advanced clinical applications and further research on the therapeutic potential of this extraordinary protein.

Overview of Lignocellulolytic Enzyme Systems with Special Reference to Valorization of Lignocellulosic Biomass.

Lignocellulosic biomass, one of the most valuable natural resources, is abundantly present on earth. Being a renewable feedstock, it harbors a great potential to be exploited as a raw material, to produce various value-added products. Lignocellulolytic microorganisms hold a unique position regarding the valorization of lignocellulosic biomass as they contain efficient enzyme systems capable of degrading this biomass. The ubiquitous nature of these microorganisms and their survival under extreme conditions have enabled their use as an effective producer of lignocellulolytic enzymes with improved biochemical features crucial to industrial bioconversion processes. These enzymes can prove to be an exquisite tool when it comes to the eco-friendly manufacturing of value-added products using waste material. This review focuses on highlighting the significance of lignocellulosic biomass, microbial sources of lignocellulolytic enzymes and their use in the formation of useful products.

Structural insight into TNF-α inhibitors through combining pharmacophore-based virtual screening and molecular dynamic simulation.

Tumor Necrosis Factor-alpha (TNF-α), a multifunctional cytokine responsible for providing resistance against infections, inflammation, and cancers. TNF-α has emerged as a promising drug target against several autoimmune and inflammatory disorders. Several synthetic antibodies (Infliximab, Etanercept, and Adalimumab) are available, but their potential to cause severe side effects has prompted them to develop alternative small molecules-based therapies for inhibition of TNF-α. In the present study, combined in silico approaches based on pharmacophore modeling, virtual screening, molecular docking, and molecular dynamics studies were employed to understand significant direct interactions between TNF-α protein and small molecule inhibitors. Initially, four different small molecule libraries (∼17.5 million molecules) were virtually screened against the selected pharmacophore model. The identified hits were further subjected to molecular docking studies. The three potent lead compounds (ZINC05848961, ZINC09402309, ZINC04502991) were further subjected to 100 ns molecular dynamic studies to examine their stability. Our docking and molecular dynamic analysis revealed that the selected lead compounds target the TNF receptor (TNFR) and efficiently block the production of TNF. Moreover, in silico ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis revealed that all the predicted compounds have good pharmacokinetic properties with high gastrointestinal absorption and a decent bioavailability score. Furthermore, toxicity profiles further evidenced that these compounds have no risk of being mutagenic, tumorigenic, reproductive and irritant except ZINC11915498. In conclusion, the present study could serve as the starting point to develop new therapeutic regimens to treat various TNF- related diseases. Communicated by Ramaswamy H. Sarma.

Construction and recombinant expression of Pseudomonas aeruginosa truncated exotoxin A in Escherichia coli.

Pseudomonas aeruginosa exotoxin A (PE) is a bacterial toxin composed of three domains namely: cell binding, translocation and enzymatic domain. The cytotoxic activity of PE is attributed to the enzymatic domain, which inhibits protein synthesis through ADP-ribosylation of EF-2. PE can be genetically modified to fight cancer. In this regard, a truncated and modified form of PE was produced that could be used for more potent immunotoxins. This modified form termed PE38KDEL was completely devoid of cell binding domain and parts of translocation domain II and Ib which are reported to be inessential for cytotoxicity of the toxin. The resultant expressed protein consisted of the essential translocation domain II and catalytic subunit (domain Ib, III). The deletions in the exotoxin A gene for truncated protein production were made via overlapping PCR extension. The amplicon was cloned in pTZ57r-T vector for DNA works and sub cloned in pET22b expression vector.  It is demonstrated here that PE38KDEL can be expressed in huge quantities in Escherichia coli by using the recombinant vector PE38KDEL/pET under control of T7 promoter and E. coli host strain BL21 (DE3) CodonPlus. The protein expression was optimized at 0.5 mM IPTG concentration for induction as soon as the OD600 nm reached 0.6 with 6 hours of post induction culturing at 37°C.  The recombinant protein was expressed both as soluble and inclusion body forms however the expression of the soluble form was more pronounced.

Evaluation of microbial potential and ripening behavoiur of preclimacteric bananas following gamma irradiation / Avaliação do potencial microbiana e amadurecem comportamento de bananas preclimacteric seguinte irradiação gama

The current study was carried out to evaluate the effects of gamma irradiation on the epiphytic microflora and ripening process of the green Dwarf Cavendish bananas harvested at the three-quarter stage of the maturity. The mature green bananas were irradiated using Cobalt-60 as the source of irradiation at different dosages of 0.5, 0.75 and 1.0 kGy. The mean life of both the experimental and control group of fruits was analyzed under ambient conditions. For all the treatments the microbial potential, the decay percent and the ripening behavior of the fruits were recorded. Results revealed that the applied radiation doses reduced the decay incidence, delayed ripening process and greatly inhibit the microbial growth (total bacterial and fungal count) thereby enhancing the shelf life of bananas. Irradiation dose of 1.0 kGy was found to be the most effective dose to positively maintain the stored bananas under ambient conditions. The mean life of bananas was extended by 14 days. The identification of the enteric bacteriaeaceae through API 20 E strips revealed the presence of Shigella sonnie on the fruit surface along with Escherichia coli and a nonfermentor spp. The dominant spoilage causing fungi identified were Aspergillus niger, Aspergillus flavus, Collotrichum musae, Fusarium oxysporum,Mucor spp, Lasiodiplodia theobromea and Rhizopus stolonifer.

O Presente estudo foi realizado para investigar os efeitos da radiação gama sobre a microflora epífita e amadurecimento das bananas Cavendish Anão verde colhidas no estádio de três quartos da maturidade. As bananas verdes maduros foram irradiadas usando Cobalto-60 como fonte de irradiação a diferentes dosagens de 0,5, 0,75 e 1,0 kGy. A vida média de ambos os grupos experimental e de controlo de frutas foi analisada sob as condições ambientes. Para todos os tratamentos a potenciais microbiana, o percentual decadência e do comportamento do amadurecimento dos frutos foram recorded.Results revelou que as doses de radiação aplicadas reduziu a incidência de podridões, atrasou processo de amadurecimento e inibir significativamente o crescimento microbiano (contagem de bactérias e fungos total), assim aumentar a vida de prateleira das bananas. dose de irradiação de 1,0 kGy foi encontrada como sendo a dose mais eficaz para manter positivamente as bananas armazenada sob condições ambientes. A vida média de bananas foi prorrogado por 14 dias. A identificação do bacteriaeaceae entérico através de API 20 E tiras revelou a presença de Shigella sonnie sobre a superfície do fruto, juntamente com Escherichia coli e um nonfermentor spp. A deterioração dominante causando fungos identificados foram Aspergillus niger, Aspergillus flavus, Collotrichum musae, Fusarium oxysporum, Mucor spp, Lasiodiplodia theobromea e Rhizopus stolonifer.