Spectroscopic studies on a natural biomarker for the identification of origin and quality of tea extracts for the development of a portable and field deployable prototype.

Even in the era of smart technologies and IoT enabled devices, tea testing technique continues to be a person specific subjective task. In this study, we have employed optical spectroscopy-based detection technique for the quantitative validation of tea quality. In this regard, we have employed the external quantum yield of quercetin at 450 nm (λex = 360 nm), which is an enzymatic product generated by the activity of ß-glucosidase on rutin, a naturally occurring metabolite responsible for tea-flavour (quality). We have found that a specific point in a graph representing Optical Density and external Quantum Yield as independent and dependent variables respectively of an aqueous tea extract objectively indicates a specific variety of the tea. A variety of tea samples from various geographical origin have been analysed with the developed technique and found to be useful for the tea quality assessment. The principal component analysis distinctly showed the tea samples originated from Nepal and Darjeeling having similar external quantum yield, while the tea samples from Assam region had a lower external quantum yield. Furthermore, we have employed experimental and computational biology techniques for the detection of adulteration and health benefit of the tea extracts. In order to assure the portability/field use, we have also developed a prototype which confirms the results obtained in the laboratory. We are of the opinion that the simple user interface and almost zero maintenance cost of the device will make it useful and attractive with minimally trained manpower at low resource setting.

Correction: Manganese neurotoxicity: nano-oxide compensates for ion-damage in mammals.

Correction for 'Manganese neurotoxicity: nano-oxide compensates for ion-damage in mammals' by Aniruddha Adhikari et al., Biomater. Sci., 2019, 7, 4491-4502, DOI: .

A Smart Nanotherapeutic Agent for in†vitro and in†vivo Reversal of Heavy-Metal-Induced Causality: Key Information from Optical Spectroscopy.

Human exposure to heavy metals can cause a variety of life-threatening disorders, affecting almost every organ of the body, including the nervous, circulatory, cardiac, excretory, and hepatic systems. The presence of heavy metal (cause) and induced oxidative stress (effect) are both responsible for the observed toxic effects. The conventional and effective way to combat heavy metal overload diseases is through use of metal chelators. However, they possess several side effects and most importantly they fail to manage the entire causality. In this study, we introduce citrate-functionalized Mn3 O4 nanoparticles (C-Mn3 O4 NPs) as an efficient chelating agent for treatment of heavy metal overload diseases. By means of UV/Vis absorbance and steady-state fluorescence spectroscopic techniques we investigated the efficacy of the NPs in chelation of a model heavy metal, lead (Pb). We also explored the retention of antioxidant properties of the Pb-chelated C-Mn3 O4 NPs using a UV/Vis-assisted DPPH assay. Through CD spectroscopic studies we established that the NPs can reverse the Pb-induced structural modifications of biological macromolecules. We also studied the in vivo efficacy of NPs in Pb-intoxicated C57BL/6j mice. The NPs were not only able to mobilize the Pb from various organs through chelation, but also saved the organs from oxidative damage. Thus, the C-Mn3 O4 NPs could be an effective nanotherapeutic agent for complete reversal of heavy-metal-induced toxicity through chelation of the heavy metal and healing of the associated oxidative stress.

Rationalization of a traditional liver medicine using systems biology approach and its evaluation in preclinical trial.

'Bottom-up', i.e., molecule to medicine strategy for the discovery of new drugs takes enormous time and cost. In most of the cases, inherent toxicity and undesired side effects of the developed drug hinder its way beyond the early stages of development. In this regard, the systems pharmacology can play an excellent role by reducing the cost and time of drug development through rationalization and/or repurposing of traditional drugs with known side effects. In the present study, our aim was to develop an integrated systems biology method for the prediction of active ingredients of a traditional medicine and their potential targets inside the body. Further, we evaluated the predictive capacity of the developed method in a preclinical animal model. Here, we have prepared a formulation (SKP17LIV01) from an extract of eight medicinal plants traditionally used as liver medicine and identified the constituents using UHPLC-MS technique. Using systems biology approach, we have rationalized the components of the formulation for potential use in the treatment of heavy metal-induced hepatotoxicity. The active ingredients and potential therapeutic targets were also predicted. A detailed biochemical, histopathological and molecular study on the mice model of lead toxicity confirms the efficacy of the formulation as per prediction by the systems pharmacology approach. The study may open a new frontier for re-discovery of drugs that are already used in traditional medicine.

Role of Nanomedicine in Redox Mediated Healing at Molecular Level.

Nanomedicine, the offspring born from the marriage of nanotechnology and medicine, has already brought momentous advances in the fight against a plethora of unmet diseases from cardiovascular and neurodegenerative to diabetes and cancer. Here, we review a conceptual framework that will provide a basic understanding about the molecular mechanism of action of a therapeutic nanomaterial inside biological milieu. In this review, we highlight how the catalytic nature of a transition metal oxide nanomaterial influences the cellular redox homeostasis, supports the cellular antioxidant defence system and reactivates the reactive oxygen species (ROS) mediated signalling to perform normal cell functions like cell cycle, differentiation, apoptosis, inflammation, toxicity, and protein interactions. With numerous examples, we describe the redox modulatory nature of d-block metal oxide nanomaterials and their biomimetic nanozyme activities to protect the mitochondria, the cellular redox mediator which prevents an organism from various diseases. This knowledge will be useful to design new nanomaterials capable of intracellular redox modulation, which in turn can be effective therapeutic agents for treatment of various unmet diseases that are beyond the ability of modern synthetic medicine.

Caspase mediated beclin-1 dependent autophagy tuning activity and apoptosis promotion by surface modified hausmannite nanoparticle.

Hidden effects of nano-materials to induced autophagy, a lysosomal degradative pathway, remain an exciting topic, in the level of material-protein interaction and subsequent cellular signaling features. Here, our studies show that surface modified hausmannite nanoparticles (Mn3 O4 NPs) can uniformly cleave/splice Beclin-1 protein and alter cellular mechanism on the emphasis of tuning autophagy and subsequently promote enhancement of apoptosis. Details investigation of Beclin-1 dependency and its uniform cleavage/splice pattern by surface modified Mn3 O4 NPs, shows tuning of cellular mechanism on emphasis of caspase mediated autophagy tuning. Our findings will also clarify the conflict between apoptosis-autophagy on the basis of its unique property derived from surface chemistry modulation, in context of Beclin-1 eminent cleavage/splice which remarks novel effect of Beclin-1 dependent tuning of autophagosomes formation and switch to enhance apoptotic index, mediates by PI3KC3 cleavage and caspase activation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1299-1310, 2017.

Conformational selection underpins recognition of multiple DNA sequences by proteins and consequent functional actions.

Recognition of multiple functional DNA sequences by a DNA-binding protein occurs widely in nature. The physico-chemical basis of this phenomenon is not well-understood. The E. coli gal repressor, a gene regulatory protein, binds two homologous but non-identical sixteen basepair sequences in the gal operon and interacts by protein-protein interaction to regulate gene expression. The two sites have nearly equal affinities for the Gal repressor. Spectroscopic studies of the Gal repressor bound to these two different DNA sequences detected significant conformational differences between them. Comprehensive single base-substitution and binding measurements were carried out on the two sequences to understand the nature of the two protein-DNA interfaces. Magnitudes of basepair-protein interaction energy show significant variation between homologous positions of the two DNA sequences. Magnitudes of variation are such that when summed over the whole sequence they largely cancel each other out, thus producing nearly equal net affinity. Modeling suggests significant alterations in the protein-DNA interface in the two complexes, which are consistent with conformational adaptation of the protein to different DNA sequences. The functional role of the two sequences was studied by substitution of one site by the other and vice versa. In both cases, substitution reduces repression in vivo. This suggests that naturally occurring DNA sequence variations play functional roles beyond merely acting as high-affinity anchoring points. We propose that two different pre-existing conformations in the conformational ensemble of the free protein are selected by two different DNA sequences for efficient sequence read-out and the conformational difference of the bound proteins leads to different functional roles.

Enhanced Charge Separation and FRET at Heterojunctions between Semiconductor Nanoparticles and Conducting Polymer Nanofibers for Efficient Solar Light Harvesting.

Energy harvesting from solar light employing nanostructured materials offer an economic way to resolve energy and environmental issues. We have developed an efficient light harvesting heterostructure based on poly(diphenylbutadiyne) (PDPB) nanofibers and ZnO nanoparticles (NPs) via a solution phase synthetic route. ZnO NPs (~20 nm) were homogeneously loaded onto the PDPB nanofibers as evident from several analytical and spectroscopic techniques. The photoinduced electron transfer from PDPB nanofibers to ZnO NPs has been confirmed by steady state and picosecond-resolved photoluminescence studies. The co-sensitization for multiple photon harvesting (with different energies) at the heterojunction has been achieved via a systematic extension of conjugation from monomeric to polymeric diphenyl butadiyne moiety in the proximity of the ZnO NPs. On the other hand, energy transfer from the surface defects of ZnO NPs (~5 nm) to PDPB nanofibers through Förster Resonance Energy Transfer (FRET) confirms the close proximity with molecular resolution. The manifestation of efficient charge separation has been realized with ~5 fold increase in photocatalytic degradation of organic pollutants in comparison to polymer nanofibers counterpart under visible light irradiation. Our results provide a novel approach for the development of nanoheterojunctions for efficient light harvesting which will be helpful in designing future solar devices.

Dynamical perspective of protein-DNA interaction.

The interactions between protein-DNA are essential for various biological activities. In this review, we provide an overview of protein-DNA interactions that emphasizes the importance of dynamical aspects. We divide protein-DNA interactions into two categories: nonspecific and specific and both the categories would be discussed highlighting some of our relevant work. In the case of nonspecific protein-DNA interaction, solvation studies (picosecond and femtosecond-resolved) explore the role environmental dynamics and change in the micropolarity around DNA molecules upon complexation with histone protein (H1). While exploring the specific protein-DNA interaction at λ-repressor-operator sites interaction, particularly OR1 and OR2, it was observed that the interfacial water dynamics is minimally perturbed upon interaction with DNA, suggesting the labile interface in the protein-DNA complex. Förster resonance energy transfer (FRET) study revealed that the structure of the protein is more compact in repressor-OR2 complex than in the repressor-OR1 complex. Fluorescence anisotropy studies indicated enhanced flexibility of the C-terminal domain of the repressor at fast timescales after complex formation with OR1. The enhanced flexibility and different conformation of the C-terminal domain of the repressor upon complexation with OR1 DNA compared to OR2 DNA were found to have pronounced effect on the rate of photoinduced electron transfer.