Subtractive Proteome Analysis of Candida albicans Divulges Promising Antifungal Targets

International Journal of Peptide Research and Therapeutics - Candida albicans is the most common nosocomial systemic fungal infections causing high mortality/morbidity. Existing antifungal...     

Biobased technologies for the efficient extraction of biopolymers from waste biomass

Bioprocess and Biosystems Engineering - Regardless of considerable progress in synthetic plastic or polymer-based industry, its low biodegradability is a critical issue. Nevertheless, natural...     

Role of curcumin and its nanoformulations in neurotherapeutics: A comprehensive review

Curcumin, a dietary polyphenol and major constituent of Curcuma longa (Zingiberaceae), is extensively used as a spice in Asian countries. For ages, turmeric has been used in traditional medicine systems to treat various diseases, which was possible because of its anti‐inflammatory, antioxidant, anticancerous, antiepileptic, antidepressant, immunomodulatory, neuroprotective, antiapoptotic, and antiproliferative effects. Curcumin has potent antioxidant, anti‐inflammatory, antiapoptotic, neurotrophic activities, which support its plausible neuroprotective effects in neurodegenerative disease. However, there is limited information available regarding the clinical efficacy of curcumin in neurodegenerative cases. The low oral bioavailability of curcumin may be speculated as a plausible factor that limits its effects in humans. Therefore, utilization of several approaches for the enhancement of bioavailability may improve clinical outcomes. Furthermore, the use of nanotechnology and a targeted drug delivery system may improve the bioavailability of curcumin. The present review is designed to summarize the molecular mechanisms pertaining to the neuroprotective effects of curcumin and its nanoformulations.     

Host phospholipase C-γ1 impairs phagocytosis and killing of mycobacteria by J774A.1 murine macrophages

Macrophages represent the first line of defense against invading Mycobacterium tuberculosis (Mtb). In order to enhance intracellular survival, Mtb targets various components of the host signaling pathways to limit macrophage functions. The outcome of Mtb infection depends on various factors derived from both host and pathogen. A detailed understanding of such factors operating during interaction of the pathogen with the host is a prerequisite for designing new approaches for combating mycobacterial infections. This work analyzed the role of host phospholipase C-γ1 (PLC-γ1) in regulating mycobacterial uptake and killing by J774A.1 murine macrophages. Small interfering RNA mediated knockdown of PLC-γ1 increased internalization and reduced the intracellular survival of both Mtb and Mycobacterium smegmatis (MS) by macrophages. Down-regulation of the host PLC-γ1 was observed during the course of mycobacterial infection within these macrophages. Finally, Mtb infection also suppressed the expression of pro-inflammatory cytokine tumor necrosis factor-α and chemokine (C-C motif) ligand 5 (RANTES) which was restored by knocking down PLC-γ1 in J774A.1 cells. These observations suggest a role of host PLC-γ1 in the uptake and killing of mycobacteria by murine macrophages.     

Psychoneurochemical Investigations to Reveal Neurobiology of Memory Deficit in Epilepsy

Pentylenetetrazole-kindling induced memory deficit has been validated in our previous study. The present study attempts a neurochemical investigation to reveal possible targets for treatment of memory deficit associated with pentylenetetrazole-kindling. Kindling was induced by administering subconvulsive dose of pentylenetetrazole (35 mg/kg; i.p.) at an interval of 48 ± 2 h. Successfully kindled animals were divided into two groups (interictal and postictal group), while non-kindled (naive) animals served as naïve group. In postictal group, animals were challenged with pentylenetetrazole (35 mg/kg) on days 5, 10, 15 and 20. Learning and memory were evaluated in all experimental groups using elevated plus maze and passive shock avoidance paradigm on days 5, 10, 15 and 20. After behavioral evaluations on day 20, all animals were sacrificed to remove their brains. Neurochemical (glutamate, GABA, norepinephrine, dopamine and serotonin) changes and acetylcholinesterase activity and total nitrite level were estimated using HPLC-FD methods and microplate reader method respectively, in discrete brain parts. The results of the neurochemical estimation demonstrated the imbalance in excitatory/inhibitory tone, reduction in monoamine level, elevated nitrosative and acetylcholinesterase activity in the cortex and hippocampus, as responsible factors for the pathobiology of learning and memory deficit in epilepsy. Restoration of these changes may be targeted for the management of memory deficit in epileptic patients.     

Inhibitors of CPH1-MAP Kinase Pathway: Ascertaining Potential Ligands as Multi-Target Drug Candidate in Candida albicans

A number of proteins contributing in pathogen’s virulence mechanisms offer a potential target for anticandidal therapeutics. CPH1 and its regulatory proteins Cst20, Hst7, Cek1 (MAPK cascade) administers filamentation and morphogenesis in human pathogenic fungus Candida albicans. These proteins are essential targets for their involvement in the successful establishment of the fungi within the host. In silico drug design using virtual screening, docking and (ADME)/Tox analysis for identification of lead compounds is an economic strategy for the development of potent anticandidal agent. The study divulged five persuasive ligands (2-O-prenyl coumaric acid, 2-nitro-4-methyl-cinnamaldehyde, 3,5-diprenyl-4-coumaric acid, VT1161, T-2307) out of 25, which collectively inhibited Cst20, Hst7, Cek1 in C. albicans. They can hence be used as natural drug leads for designing more effective inhibitors of multiple targets for C. albicans survival and progression of the disease. This study will enhance our understanding of the phenomenon “multiple targeting” and multi-target drug discovery further accelerating efficient broad-spectrum antifungal therapeutics development in near future. This study provides a good platform to eradicate the issue of “target shortage” that might facilitate the discovery of novel drugs in near future because the prolonged use of antibiotics over the years has transformed pathogenic fungus into resistant to many drugs.

     

Rifampicin Increases Expression of Plant Codon-Optimized Bacillus thuringiensis δ-Endotoxin Genes in Escherichia coli

The Protein Journal - Transgenic crops expressing Cry δ-endotoxins of Bacillus thuringiensis for insect resistance have been commercialized worldwide with increased crop productivity and...     

Multiple Drug Targeting Potential of Novel Ligands Against Virulent Proteins of Candida albicans

Systemic candidiasis is one of the most common nosocomial systemic infections causing high mortality and morbidity. Although infections caused by other Candida species are increasing the majority of candidiasis is commonly caused by Candida albicans which accounts for 40–60% of the reported cases. Current antifungal treatment regime is feeble due to persistent multiple drug resistance. Moreover, antifungal agents are mostly synthetic drugs that cause toxic side effects on immune-compromised patients. So, not only finding novel drug candidates from natural sources is necessary but to identify such compounds that have multiple targeting potential is essential. Hence, in this study, we propose to screen and identify bioactive natural compounds based on flavonoids, terpenes, and alkaloids for their potential antifungal activity. This in silico study was carried out by targeting 16 major virulent protein targets of C. albicans with 91 ligands. We have reported few ligands having multi-targeting potential and further analyzed theirs in silico pharmacokinetic profile. In silico ADMET analysis and protein–protein interaction can not only help in refining better drug candidates but also shortlist ideal protein for drug targeting.

     

Strategies for the Production of Recombinant Protein in Escherichia coli

In the recent past years, a large number of proteins have been expressed in Escherichia coli with high productivity due to rapid development of genetic engineering technologies. There are many hosts used for the production of recombinant protein but the preferred choice is E. coli due to its easier culture, short life cycle, well-known genetics, and easy genetic manipulation. We often face a problem in the expression of foreign genes in E. coli. Soluble recombinant protein is a prerequisite for structural, functional and biochemical studies of a protein. Researchers often face problems producing soluble recombinant proteins for over-expression, mainly the expression and solubility of heterologous proteins. There is no universal strategy to solve these problems but there are a few methods that can improve the level of expression, non-expression, or less expression of the gene of interest in E. coli. This review addresses these issues properly. Five levels of strategies can be used to increase the expression and solubility of over-expressed protein; (1) changing the vector, (2) changing the host, (3) changing the culture parameters of the recombinant host strain, (4) co-expression of other genes and (5) changing the gene sequences, which may help increase expression and the proper folding of desired protein. Here we present the resources available for the expression of a gene in E. coli to get a substantial amount of good quality recombinant protein. The resources include different strains of E. coli, different E. coli expression vectors, different physical and chemical agents and the co expression of chaperone interacting proteins. Perhaps it would be the solutions to such problems that will finally lead to the maturity of the application of recombinant proteins. The proposed solutions to such problems will finally lead to the maturity of the application of recombinant proteins.